bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequence of Biosynthesis of the Components of the Polyene Macrolides Candidin and Candihexin: Macrolide Aglycones as Intracellular Components
Authors: Martin Juan F. , McDaniel Lloyd E.
Published: June 2012

A sequential formation of the single components of the polyene macrolide candidin complex (heptaene) has been found. In addition to the three components occurring in the candidin complex at the end of the fermentation, two other “early” all-trans heptaene components have been characterized. They exist only during the phase of active biosynthesis of candidin. Two of the components of the polyene macrolide candihexin complex (hexaene) that have been described as lacking amino sugar were the only intracellular (mycelium-associated) components observed under conditions in which no extracellular polyene remained attached to the producing cell. The results indicate that glycosylation of the macrolide ring takes place during the secretion process.
Evaluation of a Rapid Bauer-Kirby Antibiotic Susceptibility Determination
Authors: Liberman Daniel F. , Robertson Richard G.
Published: June 2012

To reduce the incubation time requirement in the Bauer-Kirby antibiotic susceptibility test, comparisons were made of the test results at 18 to 20 h (standard) and 7 to 8 h (rapid) utilizing 100 recent clinical isolates. The zone diameters for 664 disks were monitored by using the standard classification: resistant, intermediate, or susceptible. The susceptibility determination was unchanged in 558 out of 664 instances (84.0%). An analysis of the remaining 106 sets revealed that an initial interpretation of intermediate in zone size, subsequently determined resistant or susceptible, accounted for 49 of the observed differences. The reverse changes, initial resistant or susceptible subsequently classified as intermediate, accounted for 20 of the changes. In five instances the interpretation changed from susceptible to resistant; in two cases the interpretation changed from resistant to susceptible. The remaining 30 determinations were classified as indeterminant due to (i) insufficient growth at the early (7 to 8 h) determination, and to (ii) zones which were so large that they could not be measured accurately. The data indicate that zone sizes when measured to the nearest 0.1 mm can be interpreted with reasonable accuracy and the results can be available 10 to 14 h sooner.
Activity of Pure Streptovaricins and Fractionated Streptovaricin Complex Against Friend Virus
Authors: Horoszewicz Julius S. , Rinehart Kenneth L. , Leong Susan S. , Carter William A.
Published: June 2012

Chromatographic fractionation of streptovaricin complex yields two stable components enriched (4- to 16-fold) in activity directed against the polycythemic strain of Friend virus; both components apparently contain no streptovaricins. When compared with their unfractionated parent streptovaricin complex, eight individual intact streptovaricins (A through G and J) show at least a 30-fold reduction in antiviral activity. These results further support the conclusion that the diversified biological properties of streptovaricin complex probably reside in different molecular structures.
Phosphonoacetic Acid-Resistant Herpes Simplex Virus Infection in Hairless Mice
Authors: Klein Richard J. , Friedman-Kien Alvin E.
Published: June 2012

Phosphonoacetic acid (PAA)-resistant type 1 herpes simplex virus population was isolated by repeated passage of the virus in the presence of this inhibitor. Hairless mice infected percutaneously with the inhibitor-resistant or the parental inhibitor-susceptible virus were treated intraperitoneally with PAA and 9-β-
d
-arabinofuranosyl-adenine by using several different dosage schedules. Whereas 9-β-
d
-arabinofuranosyl-adenine was effective both in the PAA-susceptible and PAA-resistant herpes simplex virus-induced skin infection, PAA suppressed only the infection induced by the parental PAA-susceptible virus.
Mechanism of Action of Anti-Influenza Benzamidine Derivatives
Authors: Fujita Haruhisa , Seto Yoshiko , Toyoshima Shigeshi
Published: June 2012

Benzamidine derivatives exhibited a high antiviral effect in vivo against influenza virus strains A2/Adachi and B/Lee. The inhibiting properties of anti-influenza benzamidine derivatives on the virus-induced inflammation undoubtedly plays an important role in the clarification of the mechanism of action of these drugs.
Effect of Oral Niridazole Treatment on Some Bacterial Infections in Mice
Authors: Collins Frank M.
Published: June 2012

Treatment of specific-pathogen-free CD-1 mice with oral doses of 10 or 100 mg of niridazole per kg of body weight given 24 h before challenge and then every other day for up to 15 days altered the growth curves for
Listeria monocytogenes, Mycobacterium bovis
(BCG Montreal),
M. tuberculosis
H37Rv, and
Salmonella enteritidis
seen in the livers and spleens of the treated animals. Niridazole in an oral dosage of 10 mg/kg reduced (but did not eliminate) tuberculin hypersensitivity in the mycobacteria-infected mice. Both delayed hypersensitivity and antimycobacterial resistance quickly returned to normal levels once the drug treatment was stopped. Niridazole treatment reduced the growth of
S. enteritidis
in both intravenously and intragastrically challenged mice; this seemed to be due to the antibacterial action of the drug on the salmonellae both in vitro and in vivo.
Inhibition by Levorphanol and Related Drugs of Amino Acid Transport by Isolated Membrane Vesicles from
Escherichia coli
Authors: Holland Mary J. C. , Simon Eric J.
Published: June 2012

Levorphanol inhibits the transport of the amino acids proline and lysine by cytoplasmic membrane vesicles derived from
Escherichia coli
. The degree of inhibition increases with increasing levorphanol concentration and ranges from 26% at 10
−6
M levorphanol to 92% at 10
−3
M levorphanol. The effect is independent of the energy source, since levorphanol inhibits proline uptake to the same extent in the presence of 20 mM
d
-lactate or 20 mM succinate and in the absence of an exogenous energy source. Levorphanol does not irreversibly alter the ability of membrane vesicles to transport proline, since incubation of membrane vesicles for 15 min in the presence of 0.25 mM levorphanol, a concentration which inhibits proline transport by more than 75%, has no effect on the rate of proline transport by these vesicles once the drug is removed. Both the maximum velocity and the

K
m

of proline transport are modified by levorphanol, hence, the type of inhibition produced by levorphanol is mixed. The inhibitor constant (

K
i

) for levorphanol inhibition of proline transport is approximately 3 × 10
−4
M. Membrane vesicles incubated in the presence of levorphanol accumulate much less proline at the steady state than do control vesicles. Furthermore, the addition of levorphanol to membrane vesicles preloaded to the steady state with proline produces a marked net efflux of proline. Levorphanol does not block either temperature-induced efflux or exchange of external proline with [
14
C]proline present in the intravesicular pool. Dextrorphan, the enantiomorph of levorphanol, and levallorphan, the
N
-allyl analogue of levorphanol, inhibit proline and lysine transport in a similar manner. Possible mechanisms of the effects of these drugs on cell membranes are discussed.
Effect of Protein Concentration and Binding on Antibiotic Assays
Authors: Peterson Lance R. , Schierl Elizabeth A. , Hall Wendell H.
Published: June 2012

Assay curves, using a disk diffusion method for the antibiotics gentamicin and cefazolin, were prepared with: saline, saline plus 10% serum, and ascitic, synovial, cerebrospinal, and pleural fluids. The curves were compared with a standard curve prepared with pooled human serum. The pH, total protein, glucose, blood urea nitrogen, sodium, potassium, calcium, phosphorus, chloride, CO
2
content, uric acid, cholesterol, bilirubin, serum glutamic oxalacetic transaminase, CPK, LDH, and alkaline phosphatase were determined and compared for all fluids. Measurements for cefazolin levels were falsely elevated in those fluids with low protein content when serum was used as a reference standard. There was a linear inverse relationship between the protein content of the fluids and the cefazolin level with serum as the standard for the assay of this highly protein-bound antibiotic. No discrepancies were observed in the assay curves for gentamicin, an antibiotic known not to be bound by serum proteins.
Herpesvirus hominis
Infection in Newborn Mice: Comparison of the Therapeutic Efficacy of 1-β-
d
-Arabinofuranosylcytosine and 9-β-
d
-Arabinofuranosyladenine
Authors: Kern Earl R. , Overall James C. , Glasgow Lowell A.
Published: June 2012

Intranasal inoculation of newborn mice with
Herpesvirus hominis
type 2 provides an experimental infection that closely resembles disseminated herpesvirus infection of human newborn infants. After inoculation of mice, the virus multiplies in the respiratory tract and is disseminated through the blood to the liver and spleen and to the brain by both a viremia and nerve route transmission. Although therapy with 1-β-
d
-arabinofuranosylcytosine (ara-C) did not reduce final mortality, it did increase the mean survival time by 1 day. This effect on the mean survival time was associated with a 1-day delay in the appearance of herpesvirus in the blood, liver, and spleen and a reduction of virus replication in lung and brain for 1 day as compared with untreated control animals. Treatment with 9-β-
d
-arabinofuranosyladenine (ara-A) likewise had no effect on final mortality, but increased the mean survival time by 2 days. Therapy with ara-A delayed or suppressed virus replication in blood, lung, liver, spleen, and brain for 2 days. Although treatment with either ara-C or ara-A in this experimental
H. hominis
type 2 infection resulted in a temporary delay and/or suppression of viral replication in several target organs, neither compound was completely effective in inhibiting viral replication or in protecting animals from eventual death due to the infection.
Pharmacokinetic Interpretation of Blood Levels and Urinary Excretion Data for Cefazolin and Cephalothin After Intravenous and Intramuscular Administration in Humans
Authors: Rattie Elisabeth S. , Ravin Louis J.
Published: June 2012

Blood levels of cefazolin and cephalothin were determined in two separate crossover studies in 20 healthy male adults, each after intravenous and intramuscular administration. Pharmacokinetic parameters were calculated from the intravenous data based upon a two-compartment open model. The rate constants controlling the distribution between the central and peripheral compartments, the overall elimination rate constants, the apparent volumes of distribution, and the fraction of the dose in the central and peripheral compartments were determined. The bioavailability was calculated to be 100% for cefazolin and cephalothin.
Epidemiology of Antibiotic and Heavy Metal Resistance in Bacteria: Resistance Patterns in Staphylococci Isolated from Populations in Iraq Exposed and Not Exposed to Heavy Metals or Antibiotics
Authors: Groves David J. , Short H. , Thewaini A. J. , Young Frank E.
Published: June 2012

Staphylococci were isolated from rural and urban populations in Iraq, which were not known to be exposed to either heavy metals or antibiotics. The antibiotic and heavy metal resistance patterns of these strains were analyzed in both mannitol-fermenting and nonfermenting strains. Over 90% of the strains were resistant to at least one of the following antibiotics: penicillin, chloramphenicol, erythromycin, tetracycline, cephalothin, lincomycin, or methicillin. In general, mannitol-fermenting strains were resistant to penicillin and cupric ions. Mannitol-negative strains were more frequently associated with mercuric ion and tetracycline resistance. Although resistance to penicillin and tetracycline can coexist, the combination of penicillin resistance and tetracycline resistance usually occurred in mannitol-negative strains. The possibility of selection of heavy metal-resistant strains due to exposure to toxic levels of methylmercury was examined. No significant increase in mercuric ion-resistant strains of staphylococci or
Escherichia coli
were detected in exposed populations as compared to control groups. The possible reasons for this result are discussed.
Evaluation of the Modified Broth-Disk Method for Determining Antibiotic Susceptibilities of Anaerobic Bacteria
Authors: Blazevic Donna J.
Published: June 2012

A total of 110 strains of anaerobic bacteria including 9 different genera was tested for antibiotic susceptibility by the modified broth-disk method of Wilkins and Thiel (1973), using prereduced media and the VPI anaerobic culture system. Results were compared with those obtained with an agar dilution technique with incubation in a GasPak jar. There was greater than 95% agreement between the two methods with ampicillin, cephalothin, chloramphenicol, and clindamycin, and 90% or greater agreement with erythromycin, penicillin, and tetracycline.
Comparative Chemotherapeutic Activity of Amphotericin B and Amphotericin B Methyl Ester
Authors: Bonner Daniel P. , Tewari Ram P. , Solotorovsky Morris , Mechlinski Witold , Schaffner Carl P.
Published: June 2012

The comparative efficacy of amphotericin B and amphotericin B methyl ester (AME) against experimental histoplasmosis, blastomycosis, cryptococcosis, and candidosis in mice was assessed by determining the effect of daily intraperitoneal therapy on 21-day survival and persistence of organisms in internal organs. AME, like amphotericin B, was effective against each of the experimental infections, but the efficacy was lower than the parent compound. For
Histoplasma
and
Blastomyces
infections the mean effective dose (ED
50
) of amphotericin B was 0.3 mg/kg, whereas the corresponding values for AME, respectively, were 2.4 and 2.8 mg/kg. For
Cryptococcus
infection the ED
50
for amphotericin B was 0.2 mg/kg compared with 2.0 mg/kg for AME. The ED
50
of amphotericin B for
Candida
infection was lower than 0.05 mg/kg and the value of AME was between 0.5 to 0.05 mg/kg. The colony counts from internal organs of the surviving animals after the therapeutic regimens were compatible with the data on survival.
Bacteriocin of a Group B Streptococcus: Partial Purification and Characterization
Authors: Tagg J. R. , Dajani A. S. , Wannamaker L. W.
Published: June 2012

The production of bacteriocin-like inhibition by two of 135 strains of group B streptococci was demonstrated during the growth of these organisms on solid nutrient media. Although a variety of gram-positive organisms was susceptible, none of a wide range of different gram-negative strains was inhibited. The active substance produced by one of these strains was extracted from cultures grown on solid media (Todd-Hewitt agar) and was shown to be bactericidal in action. This bacteriocin (streptocin B
1
) was partially purified by ammonium sulfate precipitation followed by gel filtration and ion-exchange chromatography. Production of the bacteriocin was repressed by addition of certain fermentable carbohydrates to the basic medium and enhanced by the addition of yeast extract. The bacteriocin was shown to exist in two distinct and interconvertible physical forms: a basic unit of molecular weight 10,000 and an aggregate having a molecular weight of over 200,000. The bacteriocin was inactivated by proteolytic enzymes and, although labile in alkali, it was stable to boiling in mild acids.
Improved Methods for Production, Isolation, and Assay of Two New Chloroisoxazoline Amino Acid Antitumor Antimetabolites: U-42,126 and U-43,795
Authors: Haňka L. J. , Gerpheide S. A. , Spieles P. R. , Martin D. G. , Belter P. A. , Coleman T. A. , Meyer H. F.
Published: June 2012

Improved fermentation and isolation procedures for antitumor antimetabolites U-42,126 and U-43,795 increased drug yields 30-fold. The sensitivity limit of a newly developed assay is 0.03 μg of U-42,126 and 2.0 μg of U-43,795 per ml. The in vitro antimicrobial effect of both drugs was antagonized by histidine.
Comparative Synergistic Activity of Nafcillin, Oxacillin, and Methicillin in Combination with Gentamicin Against Enterococci
Authors: Glew Richard H. , Moellering Robert C. , Wennersten Christine
Published: June 2012

The effectiveness of three semisynthetic, penicillinase-resistant penicillins alone and in combination with gentamicin was tested against 29 clinical isolates of enterococci. The minimal inhibitory concentrations of nafcillin were considerably lower than those of oxacillin and methicillin but were slightly higher than those of penicillin. At clinically achievable concentrations, the combination of nafcillin plus gentamicin produced enhanced killing against 13 of 14 strains of enterococci and was synergistic (by very rigid criteria) against 10 of 14 strains. In contrast, combinations of oxacillin plus gentamicin were synergistic against only 3 of 14 strains, and methicillin plus gentamicin produced synergistic killing against only 1 of 14 strains.
Mechanism of Chloramphenicol-Cephaloridine Synergism on
Enterobacteriaceae
Authors: Michel J. , Bornstein H. , Luboshitzky R. , Sacks T.
Published: June 2012

A synergistic in vitro bactericidal effect of combinations of chloramphenicol and beta-lactams on strains of
Enterobacteriaceae
is described. The synergism is seen with strains which are resistant to the beta-lactam and is due to chloramphenicol-induced inhibition of beta-lactamase production.
Bacteriocinogenic Clo DF13 Minicells of
Escherichia coli
Synthesize a Protein That Accounts for Immunity to Bacteriocin Clo DF13: Purification and Characterization of the Immunity Protein
Authors: Kool A. J. , Pols C. , Nijkamp H. J. J.
Published: June 2012

Cloacin DF13 inhibits protein synthesis both in vivo and in vitro by inactivation of ribosomes. In this paper we describe the purification, from purified bacteriocinogenic plasmid DF13 (Clo DF13)-harboring minicells of
Escherichia coli
, of an acidic protein (molecular weight about 10,000) that prevents the inhibition of in vitro protein synthesis by cloacin DF13. It turned out that this protein is one of three Clo DF13 plasmid-specific polypeptides that are synthesized by the noninduced Clo DF13 plasmid in minicells. Furthermore, we observed that, after induction with mitomycin C, the amount of immunity protein is only slightly increased, whereas the cloacin DF13 synthesis is increased about 40 times. These results imply that the genes that code for immunity protein and cloacin DF13 are not located in the same regulatory unit. Under noninduced conditions, apparently an excess of immunity protein is synthesized, because this amount of immunity protein is even sufficient to neutralize the strongly increased amount of cloacin after induction, since growth of induced cloacinogenic cells is continued.
Biochemical Properties of a Penicillin Beta-Lactamase Mediated by R Factor from
Bordetella bronchiseptica
Authors: Yaginuma Satoshi , Terakado Nobuyuki , Mitsuhashi Susumu
Published: June 2012

The β-lactamase specified by an R
te16
plasmid in
Bordetella bronchiseptica
was purified 200-fold by carboxymethyl-Sephadex column chromatography and electrofocusing. The enzyme has a molecular weight of 46,000 ± 3,000 and an isoelectric point of 8.3 and was highly active against phenethicillin, oxacillin, and propicillin. The enzyme activity was inhibited by sodium chloride but not by ferrous ion. The maximal enzyme activity to benzylpenicillin was observed at pH 7.0 to 7.5 and at 40 C. It is concluded that this enzyme is different from the R-mediated β-lactamases, i.e., the type I and type II β-lactamases which have been classified in previous papers.
Nalidixic Acid: an Antibacterial Paradox
Authors: Crumplin G. C. , Smith J. T.
Published: June 2012

Nalidixic acid was found to be most bactericidal against various species of gram-negative bacteria at 50 to 200 μg/ml. With all species tested, increases in the concentration of nalidixic acid above this range reduced, rather than increased, its bactericidal effect so that, at levels in the region of 400 μg/ml, the drug was relatively bacteriostatic. Therefore, the mode of action of nalidixic acid at various concentrations was investigated. It was found that at the most bactericidal concentration deoxyribonucleic acid synthesis, but no ribonucleic acid (RNA) or protein synthesis, was inhibited. However at higher concentrations, where the drug is least bactericidal, both RNA and protein synthesis were found to be inhibited. Results are presented which suggest that the protein synthesis inhibition is a secondary manifestation of the ability of the drug to inhibit RNA synthesis, and that of RNA synthesis is most likely the second target site for the action of the drug when bacteria are exposed to it in high concentrations. The clinical implications of these findings are discussed.
Mecillinam (FL 1060), a 6β-Amidinopenicillanic Acid Derivative: In Vitro Evaluation
Authors: Tybring L.
Published: June 2012

Mecillinam (formerly called FL 1060), a novel 6β-amidinopenicillanic acid derivative, showed markedly higher activity than ampicillin against clinical isolates of
Enterobacteriaceae
. The mode of action of mecillinam is different from that of ampicillin and consequently no intrinsic cross-resistance between the two antibiotics was observed. Mecillinam is inactivated by β-lactamases but is generally more stable than ampicillin; thus an apparent cross-resistance exists for strong β-lactamase producers. The protein binding was low and the activity was relatively independent of pH between 5.5 and 8.0. Slow-growing, insensitive variants of
Escherichia coli
could be selected but these were not stable. The frequency of insensitive variants was affected by the sodium chloride concentration in the medium.
Mecillinam (FL 1060), a 6β-Amidinopenicillanic Acid Derivative: Bactericidal Action and Synergy In Vitro
Authors: Tybring L. , Melchior N. H.
Published: June 2012

A newly described 6β-amidinopenicillanic acid derivative, mecillinam (formerly called FL 1060), showed a high in vitro activity against
Enterobacteriaceae
. The effect on
Escherichia coli
was bactericidal and was due to lysis of the cells. The longer the culture grew under the influence of mecillinam or the lower the inoculum, the greater the bactericidal effect. The morphology of the cells changed towards large spheric forms (2 to 5 μm) under the influence of mecillinam. Consequently a great discrepancy between the optical density and the viable count was seen. The morphologically abnormal cells could be protected against lysis in vitro by addition of ionized compounds such as sodium chloride. Abnormal cells were more sensitive to ampicillin than normal cells. As expected synergy could be demonstrated between mecillinam and ampicillin. This was marked under experimental conditions where the abnormal cells were protected against lysis.
Susceptibility of
Pseudomonas aeruginosa
to Tobramycin or Gentamicin Alone and Combined with Carbenicillin
Authors: Anderson Edwin L. , Gramling Patricia K. , Vestal Patricia R. , Farrar W. Edmund
Published: June 2012

To explore more effective therapy for
Pseudomonas aeruginosa
, 264 recent clinical isolates were tested by agar dilution using gentamicin and tobramycin alone and combined with carbenicillin to seek synergistic effects. Synergism was defined as a fourfold or greater decrease in the minimal inhibitory concentration of each drug in a pair. At a concentration of 3.12 μg/ml, gentamicin inhibited 73% of the strains and tobramycin inhibited 98%. The gentamicin-carbenicillin combination was synergistically active against 57% of the strains, and tobramycin-carbenicillin was active against 46%. The effect did not correlate with either susceptibility or resistance to gentamicin or tobramycin alone. The data suggest that tobramycin or tobramycin plus carbenicillin may provide alternate therapy where susceptibility to gentamicin or synergism between gentamicin and carbenicillin cannot be demonstrated; however, the degree of susceptibility to either aminoglycoside antibiotic alone cannot be used to predict a synergistic effect.
Binding of Bacteriocin Clo DF13 to Clo DF13 Plasmid Deoxyribonucleic Acid In Vivo and In Vitro
Authors: Veltkamp E. , Blankevoort R. , Nijkamp H. J. J.
Published: June 2012

The bacteriocinogenic plasmid Clo DF13 is present in
Escherichia coli
to the extent of 10 copies per cell. A complex of Clo DF13 plasmid deoxyribonucleic acid (DNA) and protein can be isolated from cells. Treatment of the complex with ionic detergents or proteases dissociates the complex but does not convert any supercoiled Clo DF13 DNA to the open circular form, indicating that this complex is not a relaxation complex. The complex is stable in 0.5 M NaCl and contains one polypeptide species. The protein, present in the complex, appeared to be bacteriocin Clo DF13 for the following reasons: (i) the protein is de novo synthesized in Clo DF13-harboring minicells, indicating that this protein is Clo DF13 specific; (ii) this protein shows bacteriocinogenic activity on a bacteriocin Clo DF13-susceptible indicator strain; (iii) this protein has the same molecular weight (60,000) as bacteriocin Clo DF13. DNA-protein binding experiments, involving QAE-Sephadex column chromatography and nitrocellulose membrane filters, demonstrate that bacteriocin Clo DF13 has also affinity in vitro for Clo DF13 DNA. Membrane filter binding experiments revealed that bacteriocin Clo DF13 does not interact with other DNA species, such as ColE1 DNA, yeast DNA, calf thymus DNA, φX174 DNA, and also not with denatured Clo DF13 DNA. In addition no binding to Clo DF13 DNA of a related bacteriocin, colicin E3, could be detected. These results indicate that the binding of bacteriocin Clo DF 13 to double-stranded Clo DF13 DNA is very specific.
Mode of Action of Polymyxin B: Physiological Studies with a
Bacillus subtilis
-Resistant Mutant
Authors: Galizzi A. , Cacco G. , Siccardi A. G. , Mazza G.
Published: June 2012

Polymyxin B resistance in
Bacillus subtilis
can be suppressed by the synergistic action of lysozyme or of an analogous cell wall lytic activity released by
B. subtilis
spores during germination.

Such a synergistic effect is probably due to partial cell-wall digestion by lysozyme that allows polymyxin to reach its site of action and is therefore distinct from the analogous synergistic effect described by other authors in
Escherichia coli
. In the latter case polymyxin B probably damaged the outer membrane, allowing lysozyme to reach and digest the cell wall.
Specificity of the Antiviral Agent Calcium Elenolate
Authors: Heinze John E. , Hale Arthur H. , Carl Philip L.
Published: June 2012

Calcium elenolate, an antiviral agent which inhibits reverse transcriptases, inhibits the growth of chicken embryo fibroblast cells, as well as
Echerichia coli
and
Bacillus subtilis
strains. The drug in vitro inhibits
E. coli
deoxyribonucleic acid (DNA) polymerase II and DNA polymerase III holoenzyme, as well as several unrelated enzymes. The usual DNA polymerase assay components, with the exception of spermidine, have no effect on the observed inhibition. Inhibition of DNA polymerase II by the drug appears to be due to a direct and irreversible effect on the enzyme. However, DNA synthesis in
E. coli
is no more susceptible to the drug than is the increase in cell mass. These results suggest that calcium elenolate is an inhibitor of rather low specificity.
Antimicrobial Therapy of Experimental Enterococcal Endocarditis
Authors: Hook Edward W. , Roberts Richard B. , Sande Merle A.
Published: June 2012

The successful therapy of enterococcal endocarditis requires prolonged administration of synergistic antibiotic combinations. Controversy has arisen regarding optimal therapy (i) when the organism possesses high-level streptomycin resistance, and (ii) when the patient is allergic to penicillin. This study examines these questions in vitro and in a rabbit model of enterococcal endocarditis. The combination of penicillin with either streptomycin or gentamicin increased the rate of bacterial killing in vitro and in vivo when compared with penicillin alone (
P
< 0.05) when the test strain was relatively susceptible to streptomycin (minimal inhibitory concentration, 128 μg/ml). Only the combination of penicillin and gentamicin was consistently more effective than penicillin alone (
P
< 0.01) when the test strain was highly resistant to streptomycin (minimal inhibitory concentration > 150,000 μg/ml). The combination of vancomycin and streptomycin was more rapidly bactericidal than vancomycin alone in vitro and in the animal model against the streptomycin-susceptible strain (
P
< 0.01). The relative rate of in vitro bacterial killing by various antibiotics and combinations was predictive of the efficacy of these drugs in eradicating enterococci from cardiac vegetation in experimental endocarditis.
Comparison of the Antiviral Effects of 5-Methoxymethyl-deoxyuridine with 5-Iododeoxyuridine, Cytosine Arabinoside, and Adenine Arabinoside
Authors: Babiuk Lorne A. , Meldrum Blair , Gupta V. Sagar , Rouse Barry T.
Published: June 2012

The antiviral activity of 5-methoxymethyl-2′-deoxyuridine (MMUdR) was compared with that of 5-iodo-2′-deoxyuridine (IUdR), cytosine arabinoside (Ara-C), and adenine arabinoside (Ara-A). At concentrations of 2 to 4 μg/ml, MMUdR was inhibitory to herpes simplex virus type 1, but concentrations as high as 128 μg/ml were not inhibitory to three other herpesviruses tested (equine rhinopneumonitis virus, murine cytomegalovirus, and feline rhinopneumonitis virus) or to vaccinia virus. The other nucleosides, in contrast, were inhibitory at similar concentrations (1 to 8 μg/ml) against all viruses tested. The inhibition of HSV-1 by MMUdR appeared to be the result of interference with virus replication rather than the result of drug toxicity to host cells. The drug was not toxic to host cells at 100 times the antiviral concentrations, and pretreatment of host cells with high concentrations of MMUdR had no effect on subsequent virus replication. Combination of MMUdR with either IUdR, Ara-A, or Ara-C gave an enhanced antiviral effect, suggesting that the mechanism of action of MMUdR is different from that of the other three drugs. Antiviral indexes were calculated for each compound and were found to be >250, 80, 40, and 8 for MMUdR, IUdR, Ara-A, and Ara-C, respectively. These were defined as the minimum dose at which toxicity was observed microscopically divided by the dose which reduced plaque numbers by 50%.
Influence of Subtherapeutic Levels of Oxytetracycline on
Salmonella typhimurium
in Swine, Calves, and Chickens
Authors: Evangelisti D. G. , English A. R. , Girard A. E. , Lynch J. E. , Solomons I. A.
Published: June 2012

Subtherapeutic levels of oxytetracycline in animal feeds have been evaluated to determine their influence on the relative quantity, prevalence, shedding, and antibiotic susceptibility of
Salmonella typhimurium
in swine, calves, and chickens, when compared with nonmedicated controls. The medicated groups were fed rations containing oxytetracycline commencing 5 days prior to oral inoculation with
S. typhimurium
and continuing through a 28-day post-inoculation period. Colonization of
S. typhimurium
occurred in all three animal species as evidenced by clinical signs of infection and/or colony counts in feces measured on seven separate occasions over the 28-day observation period. The accumulated data demonstrate that the subtherapeutic use of oxytetracycline did not bring about any increases in the quantity, prevalence, or shedding of
S. typhimurium
in swine, calves, and chickens. In fact, the medication generally brought about a decrease in the percentage of animals carrying
S. typhimurium
during the study period. In contrast to results in swine and calves, there was a significant occurrence of
S. typhimurium
resistance to oxytetracycline in chickens. Resistant colonies were isolated from chickens sporadically but never on more than two consecutive test periods. These isolates were also resistant to streptomycin, but not to the other six antibiotics tested. The population of resistant
S. typhimurium
isolated from medicated chickens was no larger than that of susceptible
S. typhimurium
isolated from the nonmedicated animals. It is concluded that no evidence has been obtained which would relate the continuous low-level feeding of oxytetracycline for a 4-week period to an increased incidence of disease in animals or as a hazard to humans.
In Vitro Activity and Pharmacokinetics in Patients of Cefamandole, a New Cephalosporin Antibiotic
Authors: Shemonsky Natalie K. , Carrizosa Jaime , Levison Matthew E.
Published: June 2012

Cefamandole nafate, a new cephalosporin for parenteral use, was evaluated in vitro against 231 recent clinical isolates and in 12 patients. Cefamandole had activity equivalent to cefazolin against
Staphylococcus aureus, Escherichia coli
, and
Klebsiella pneumoniae
. Cefamandole was more active than cephalothin or cefazolin against
Proteus mirabilis
. Both cefamandole and cefazolin were as active as cephalothin against
S. aureus
, were slightly more active against
K. pneumoniae
, and were considerably more active against
E. coli
. All strains of indole-positive
Proteus
sp. were inhibited by 6.3 μg of cefamandole per ml but only 20% were inhibited by 25 μg of cefazolin or cephalothin per ml. Eighty-eight percent of
Enterobacter
sp. was inhibited by 25 μg of cefamandole per ml, but only 20 and 5% were inhibited by the same concentration of cefazolin and cephalothin, respectively. Peak levels of cefamandole ranged from 6.0 to 110 μg/ml in serum and levels ranged from 440 to 16,800 μg/ml in a 4- to 6-h collection of urine after a 500-mg or 1-g intramuscular dose (6.1 to 17.3 mg/kg) in patients with endogenous creatinine clearances of ≥31 ml/min. These levels were done after the first dose, at mid-therapy, and at the end of therapy. There was no evidence of accumulation with the 500-mg or 1-g dose given every 4 to 6 h. The percentage of the dose excreted in the urine within the first 4 to 6 h after administration of cefamandole was ≥43%. The half-life of cefamandole in serum was 49 to 126 min.
Drug-Resistant
Leptomonas
: Cross-Resistance in Trypanocide-Resistant Clones
Authors: Bacchi C. J. , Lambros C. , Ellenbogen B. B. , Penkovsky L. N. , Sullivan W. , Eyinna E. E. , Hutner S. H.
Published: June 2012

A
Leptomonas
of insect origin was highly susceptible to several standard trypanocides and leishmanicides in vitro. Resistance was induced to some of these drugs; clones were isolated from each strain. Cross-resistance patterns of the clones were derived for diamidines, quinapyramine (Antrycide), acriflavin, phenanthridines, and other drugs active against trypanosomes and leishmanias. Clones tested included two each that were resistant to acriflavin, Antrycide, diminazene aceturate (Berenil), and pentamidine and one that was resistant to stilbamidine. Appreciable cross-resistance was evident for all clones. Differences were observed between clones from the same parent strain. Collateral susceptibility towards isometamidium and oxophenarsine was detected in most clone-derived populations. In clones passaged without drug to test for drug fastness, acriflavin and pentamidine clones lost resistance within 10 transfers, whereas Berenil and Antrycide clones retained considerable resistance after 20 to 30 subcultures without drug. Considerations of differences in life cycles suggest that the clone collection may be useful in screening for agents effective against leishmanias and stercorarian trypanosomes rather than against salivary trypanosomes.
Distribution of R Plasmids Among the O-Antigen Types of
Escherichia coli
Isolated from Various Clinical Sources
Authors: Petrocheilou V. , Richmond M. H.
Published: June 2012

A total of 655
Escherichia coli
strains from various clinical sources were O-antigen typed, and the serological properties were correlated with R-plasmid carriage. Of the 655 strains, 224 were resistant to one or more antibiotics and 148 of these carried R plasmids. The distribution of O-antigen types among the susceptible strains was similar to that reported previously by others in England. The O-antigen types among the R
+
strains showed some similarities to those found in susceptible strains, but O-antigen types O8, O9, O17, O18 and, perhaps, O101 and O107 were more common in the R
+
than in the susceptible series. There is therefore some overlap between the O-antigen types of
E. coli
prevalent in R
+
strains from clinical cases and from human and animal fecal sources.
Binding of
N
-Substituted Erythromycylamines to Ribosomes
Authors: Vince Robert , Weiss David , Pestka Sidney
Published: June 2012

Several
N
-substituted erythromycylamines were evaluated for their ability to inhibit the binding of [
14
C]erythromycin to ribosomes. The association and dissociation constants for the binding of each compound to
Escherichia coli
ribosomes were determined. These studies have resulted in the development of three types of probes for topological studies of the erythromycin-binding site and the ribosome: the chemically reactive bromoacetamido, the photoreactive
N
-(2)-nitro-4-azidophenyl)glycinamido, and the fluorescent fluorescein isothiocyanate derivatives of 9(S)-erythromycylamine.
Micromonospora
-Produced Gentamicin Components
Authors: Lee B. K. , Condon R. G. , Wagman G. H. , Katz E.
Published: June 2012

After the chromatographic separation of [
methyl
-
14
C]gentamicin major (C) components from a large-scale radioactive fermentation (Lee et al., 1974), [
methyl
-
14
C]gentamicin minor (polar) components (A, B, B
1
, X
2
, and G-418) were isolated from subsequent chromatography of the remaining antibiotic mixture. When
l
-[
methyl
-
14
C]methionine was added at the onset of biosynthesis of the gentamicin components, incorporation of label into the minor components preceded incorporation into the major components. Degradation occurred when [
methyl
-
14
C]gentamicin major components (C
1
, C
2
and C
1
a) were added respectively to the gentamicin-producing culture medium and shaken.
Action of Polymyxin B on Bacterial Membranes: Phosphatidylglycerol- and Cardiolipin-Induced Susceptibility to Polymyxin B in
Acholeplasma laidlawii
B
Authors: Teuber Michael , Bader Johann
Published: June 2012

To identify the polymyxin receptor molecules in the membranes of living microorganisms, fusion of intact
Acholeplasma laidlawii
B with lipid vesicles was investigated according to the procedure of Grant and McConnell (1973). The naturally polymyxin-resistant
A. laidlawii
B was treated with phospholipid vesicles prepared from purified phospholipids of the polymyxin-susceptible
Salmonella typhimurium
G30.
A. laidlawii
B absorbed between 15 and 45% of its own lipid content of the added tritium-labeled phospholipids without loss of viability. Association with the acidic components phosphatidylglycerol and cardiolipin produced a 10- to 30-fold increase in polymyxin susceptibility, which was not obtained with egg-phosphatidylcholine and mixed phosphatidylcholine-phosphatidylethanolamine vesicles. The polymyxin-sensitized cells bound 12 times more radioactive antibiotic than resistant cells. The phosphatidylglycerol-induced susceptibility was abolished by serum fraction V (Cohn) proteins.
Chelocardin-Inducible Resistance in
Escherichia coli
Bearing R Plasmids
Authors: Chabbert Yves A. , Scavizzi Maurice R.
Published: June 2012

Two plasmid-linked tetracycline resistance characters,
tet
A and
tet
B, were distinguishable in part, according to the level of resistance they conferred to minocycline (<3 μg/ml for
tet
A; >6 μg/ml for
tet
B).
Escherichia coli
K-12 strains that harbored the
tet
B character were also resistant to tetracycline but susceptible to chelocardin. In such
tet
B strains, subinhibitory concentrations of tetracycline could induce resistance to chelocardin as well as to otherwise inhibitory concentrations of tetracyclines. Chelocardin itself was ineffective as an inducer and therefore could be used to select constitutively resistant mutants.
E. coli
K-12 strains harboring the
tet
A character were also resistant to tetracycline and susceptible to chelocardin; tetracycline did not induce resistance to chelocardin in these strains.
Sulfamethoxazole-Trimethoprim-Polymyxin Therapy of Serious Multiply Drug-Resistant
Serratia
Infections
Authors: Thomas Frank E. , Leonard John M. , Alford Robert H.
Published: June 2012

Nonpigmented multiply drug-resistant
Serratia marcescens
caused an extensive outbreak of infection at the Nashville Veterans Administration Hospital. Isolates were of one serotype resistant to all currently available antimicrobial agents for therapy of systemic infections except for occasional susceptibility to chloramphenicol and kanamycin. Frequently strains were susceptible to nalidixic acid, and all were susceptible to amikacin (BB-K8). Drug-resistant strains caused 130 infections, 12 bacteremias, and 7 infection-associated deaths. Combinations of antimicrobial agents were evaluated for synergism against
Serratia
strains from infected patients. “Checkerboard” isobolograms indicated in vitro static synergism between sulfamethoxazole, trimethoprim, and polymyxin (STP). Killing curves using clinically achievable concentrations of STP verified the bactericidal effect of STP against these strains. In a daily dosage of 1,600 mg of sulfamethoxazole and 320 mg of trimethoprim orally in combination with 100 to 300 mg of colistimethate parenterally, serum cidal levels at 1:8 or greater were achieved in five of six patients. Clinical improvement or microbiological cure was effected in four of six patients. STP may be potentially useful for selected
Serratia
infections for which single agents are unavailable or ineffective.
Antimicrobial Susceptibilities of Shigellae Isolated in Houston, Texas, in 1974
Authors: Byers Patricia A. , Dupont Herbert L. , Goldschmidt Millicent C.
Published: June 2012

One hundred seventy-three strains of shigellae (113
Shigella sonnei
, 56
S. flexneri
, and four others) isolated in Houston during 1974 were tested for susceptibility to commonly used and newer antimicrobial agents. Forty-five percent of
S. sonnei
strains were susceptible to ampicillin, whereas 93% of
S. flexneri
strains were susceptible to that agent.
S. sonnei
and
S. flexneri
strains were equally susceptible to tetracycline (35 and 33%, respectively). All 173 strains were uniformly susceptible to quinoline drugs (cinoxacin, oxolinic acid, and nalidixic acid) and to trimethoprim-sulfamethoxazole. This study supports recent suggestions that the initial therapy of bacillary dysentery no longer should be ampicillin or tetracycline. It remains for field testing to determine whether quinoline agents or trimethoprim-sulfamethoxazole will be the treatment of choice.
In Vitro Activity of BL-S640 Against Gram-Negative Bacilli and
Staphylococcus aureus
Compared with Activity of Four Other Semisynthetic Cephalosporins
Authors: Vuye A. , Pijck J. , Soep H.
Published: June 2012

The in vitro activity of BL-S640 (cefatrizine) was determined against 674 recent clinical isolates of
Staphylococcus aureus
and
Enterobacteriaceae
. Activity against
S. aureus
was less than that of cephapirin, cephalothin, and cefazolin, but greater than that of cephalexin. Activity against gram-negative isolates was variable: BL-S640 was slightly less potent than cefazolin against
Escherichia coli
and
Klebsiella
, but more active than the other compounds. As for the more resistant gram-negative genera, BL-S640 was significantly superior to the control cephalosporins. The effect of inoculum size on the antibacterial activity was moderate for most organisms except
Enterobacter, Providencia stuartii
, and indole-positive
Proteus
, the median minimal inhibitory concentrations of which were 6 to 27 times lower when determined with a 10
−4
-diluted culture compared with the undiluted one. The stability in aqueous solution at 37 C was remarkably high at the lower pH values, but low at the neutral point.
In Vivo Synergy Between 6β-Amidinopenicillanic Acid Derivatives and Other Antibiotics
Authors: Grunberg E. , Cleeland R. , Beskid G. , DeLorenzo W. F.
Published: June 2012

Both an oral and a parenteral form of a 6β-amidinopenicillanic acid derivative were found to have appreciable activity against gram-negative bacteria and poor activity against gram-positive bacteria in vivo. When administered orally or parenterally, definite synergy was demonstrated between the amidinopenicillins and ampicillin, amoxicillin, benzylpenicillin, cefazolin, or carbenicillin in infections with a number of gram-negative bacteria, including
Klebsiella, Enterobacter, Escherichia, Proteus, Salmonella
, and
Haemophilus
species in mice. Synergy was also observed between the parenteral amidinopenicillin and benzylpenicillin in the
Staphylococcus aureus
infection but not in infections with other gram-positive organisms. No synergy was demonstrated between the parenteral amidinopenicillin and erythromycin or oxytetracycline in infections with gram-positive or gram-negative organisms. Synergy between the parenteral amidinopenicillin and gentamicin was observed only in the case of
Escherichia coli
.
Bactericidal Action of Dapsone Against
Mycobacterium leprae
in Mice
Authors: Levy Louis
Published: June 2012

Dapsone (4,4′-diaminodiphenylsulfone), incorporated into the mouse chow in a concentration of 0.1 g/100 g of diet, was administered for 1 week to mice in which
Mycobacterium leprae
had multiplied to the level of 10
6
organisms/footpad.
M. leprae
were harvested from these and also from control mice, diluted serially, and inoculated into additional mice. The organisms recovered from untreated mice multiplied in passage with a mean doubling time of 12.2 days, and 35% or more of the inoculated organisms were viable, i.e., capable of infecting mice. Growth curves of
M. leprae
recovered from dapsone-treated animals lagged behind those of organisms from control animals by an average of 78 days, equivalent to 98.8% killing. Foot-by-foot harvests showed that only 0.2% of the
M. leprae
recovered from treated mice were viable, suggesting that treatment of mice with dapsone had been accompanied by killing of 99.4% of the viable
M. leprae
.
Safety of the Bolus Administration of Gentamicin
Authors: Mendelson J. , Portnoy J. , Dick V. , Black M.
Published: June 2012

A study was done to assess the safety of gentamicin administration by a bolus method. A total of 63 patients were randomly treated with intravenous gentamicin by bolus administration (3 to 5 min) and by slow infusion (2 h). Serum gentamicin levels were measured. Renal and audiovestibular function were monitored. Pure-tone audiometry was performed at the beginning, on day 3, and at the end of therapy. The study revealed that the bolus administration was safe and nontoxic.
Antibacterial Activity of Cefuroxime, a New Cephalosporin Antibiotic, Compared with That of Cephaloridine, Cephalothin, and Cefamandole
Authors: Eykyn Susannah , Jenkins Clare , King Anna , Phillips Ian
Published: June 2012

The in vitro activity of cefuroxime, a new cephalosporin derivative, was compared with that of cephaloridine, cephalothin, and cefamandole against strains of gram-positive and gram-negative bacteria recently isolated from clinical sources. Cefuroxime showed very similar activity to cefamandole against
Staphylococcus aureus, Haemophilus influenzae
, and most members of the
Enterobacteriaceae
. It was more active than cefamandole against gonococci, pneumococci, and most streptococci. Increasing the inoculum size appeared to have less effect on the minimum inhibitory concentrations of cefuroxime for gram-negative bacilli than has been found with the other cephalosporin derivatives, and minimum bactericidal concentrations of cefuroxime were only marginally greater than minimum inhibitory concentrations.
Penicillin-Induced Lysis of
Escherichia coli
in Medium That Does Not Support Sustained Growth
Authors: Berg Claire M. , Anderson Scott V.
Published: June 2012

Exponentially growing cells of an
Escherichia coli
auxotroph that are washed and resuspended in buffer containing a carbon source undergo sufficient growth to render them susceptible to penicillin-induced lysis, even in the absence of the required metabolite. This lysis is probably responsible for the reduction in intracellular enzyme activity previously attributed to a direct effect of penicillin upon the enzyme.