bluuebunny/crossref_metadata_2025 huggingface dataset:
Binding of Dihydrostreptomycin to
Escherichia coli
Ribosomes: Characteristics and Equilibrium of the Reaction
Authors: Chang F. N. , Flaks Joel G.
Published: June 2012

The binding of dihydrostreptomycin to ribosomes and ribosomal subunits of a number of different
Escherichia coli
strains was studied, and the Mg
2+
and
p
H dependence, as well as the effect of salts and polynucleotides, was determined. The only requirement for binding with ribosomes and subunits from susceptible strains was 10 m
m
Mg
2+
. Monovalent salts weakened the binding in a manner similar to the effects on ribonucleic acid secondary structure, and this was antagonized to some extent by increased amounts of Mg
2+
. Bound dihydrostreptomycin could be readily exchanged by streptomycin and any antibiotically active derivative, but not by fragments of the antibiotic or any other aminoglycoside. With native (run-off) 70
S
ribosomes from streptomycin-susceptible strains, the binding was rapid and relatively temperature independent over the range from 0 to 37 C. Polynucleotides did not stimulate the binding. With concentrations of dihydrostreptomycin up to 10
−5
m
, greater than 95% of native 70
S
ribosomes bound exactly 1 molecule of the antibiotic tightly, with a
K
diss
for the bound complex at 25 C of 9.4 × 10
−8
m
. The following thermodynamic parameters were found for the binding with 70
S
ribosomes at 25 C:ΔG° = −9.6 kcal/mole, ΔH° = −6.2 kcal/mole, and ΔS° = +11.4 entropy units/mole. Differences in affinity for the antibiotic were found between ribosomes of K-12 strains and those of other
E. coli
strains. There was insignificant binding to 70
S
ribosomes or subunits from streptomycin-resistant or -dependent strains, and to 50
S
subunits from susceptible strains. The binding to 30
S
subunits from susceptible strains was weaker by an order of magnitude than that to the 70
S
particle, with a
K
diss
at 25 C of 10
−6
m
. Polyuridylic acid stimulated this binding slightly but did not influence the affinity of the bound molecule. At antibiotic concentrations above 10
−5
m
, streptomycin-susceptible 70
S
and 30
S
particles bound additional molecules of the antibiotic, and binding also occurred to ribosomes from streptomycin-resistant and -dependent strains, as well as to 50
S
subunits from all strains.
K
diss
for all of these binding equilibria were [Formula: see text] 10
−4
m
. This weaker non-specific binding coincided with the beginning of aggregation phenomena involving the particles, and occurred at sites distinct from the single site which binds the antibiotic tightly. This latter site was completely lost after the one-step mutation to high-level resistance or dependence.
Automatic Radiometric Measurement of Antibiotic Effect on Bacterial Growth
Authors: DeBlanc Harold J. , Charache Patricia , Wagner Henry N.
Published: June 2012

A new method for rapid, automatic radiometric measurement of antibiotic effects on bacterial growth was developed and compared with a conventional broth dilutior technique. The radiometric method measures the amount of radioactive CO
2
generated by the bacterial metabolism of
14
C-glucose in the presence of antibiotics. Antibiotic effect on bacterial growth was standardized by measuring the evolution of
14
CO
2
3 hr after inoculation. This measurement was found to be quantitatively related to increasing concentration of antibiotic provided the organism was susceptible to the antibiotic tested. In 50 of 179 experiments (28%), each testing one organism against serial concentrations of an antibiotic, the concentration of antibiotic producing a 50% reduction of
14
CO
2
within 3 hr after inoculation in comparison with a control culture was the same as the minimal inhibitory concentration (MIC) determined by the broth dilution technique. In 129 experiments (72%), the antibiotic concentrations inhibiting
14
CO
2
release to 50% of the control level were less than the MIC values. Results of the radiometric method were related to those of the broth dilution method by constant factors characteristic of the organism and antibiotic tested. Our results indicate that the radiometric method provides a reproducible, quantitative, rapid, and sensitive measurement of the inhibitory effects of antibiotics on bacterial growth. The constant relationship between the results of the radiometric and conventional technique should facilitate the adaptation of the automated method to clinical testing of antibiotic susceptibility.
Silver Sulfadiazine: Effect on the Growth and Metabolism of Bacteria
Authors: Rosenkranz Herbert S. , Carr Howard S.
Published: June 2012

Even though the addition of silver sulfadiazine (AgSu) to purified deoxyribonucleic acid (DNA) results in the formation of AgSu-DNA complexes, no such complexes were detected in bacteria treated with AgSu. AgSu blocked macromolecular syntheses in treated bacteria, DNA synthesis being slightly more sensitive to this inhibitory action. The ribosomes, ribonucleic acid, and DNA isolated from treated cells were normal qualitatively. Bacteria deficient in DNA polymerase were not more sensitive than their parent strain to the lethal action of AgSu. Radioactive AgSu was localized mainly in the cytoplasmic membrane fraction of treated cells.
Metabolic Inhibition as an Index of Bacterial Susceptibility to Drugs
Authors: DeLand Frank H. , Cohen Michael
Published: June 2012

Detection of bacterial growth by measuring the release of
14
CO
2
from the metabolism of uniformly labeled
14
C-glucose has proven to be accurate, sensitive, and rapid. The inhibition of glucose metabolism by antibiotics as an index of bacterial susceptibility was evaluated based on radiometric methodology. Bacterial dose-response curves to antibiotics were defined. The susceptibility to drugs was determined within several hours after inoculation of the cultures. The pentose phosphate shunt appeared to be the major metabolic pathway involved during this period. There was a consistent relationship between the dose-response curves determined by the inhibition of glucose metabolism and the minimal inhibitory concentrations determined by a serial broth dilution technique. Inhibition of metabolism as an index of bacterial susceptibility to drugs appears to be valid, rapid, and readily applicable to available automation.
Is There Complete Cross-Resistance of Gram-Negative Bacilli to Gentamicin and Tobramycin?
Authors: Crowe C. C. , Sanders E.
Published: June 2012

No cross-resistance between gentamicin and tobramycin was found among 19 recent clinical isolates representing four genera of gram-negative bacilli.
Clotrimazole (Bay b 5097): In Vitro and Clinical Pharmacological Studies
Authors: Burgess M. A. , Bodey Gerald P.
Published: June 2012

Clotrimazole (Bay b 5097) is a new synthetic antifungal drug with in vitro activity against
Candida
spp.,
Torulopsis glabrata
, and
Saccharomyces
spp. Pharmacological studies in man after the oral administration of 1.5 and 3 g of clotrimazole produced mean peak concentrations in the serum of 1.16 and 1.29 μg/ml, respectively, 2 hr after administration. In six patients taking 1.5 g of clotrimazole every 6 hr, there was a progressive decline in the serum concentrations after administration of a dose on days 1, 4, and 8. Nine other patients begun on a similar schedule manifested gastrointestinal symptoms attributed to the clotrimazole and were unable to complete the study. Concentrations of active drug in the urine were less than 1% of the administered dose.
Inhibition of β-Lactamases by β-Lactam Antibiotics
Authors: O'Callaghan Cynthia H. , Morris A.
Published: June 2012

The inhibitory properties of a selected number of β-lactam antibiotics were studied, with the use of three distinct types of β-lactamases. The three enzymes were found to be distinguishable on the basis of their susceptibility to inhibition. Not one of the potential inhibitors tested was found to be a potent inhibitor of all three enzymes, but nafcillin possessed the broadest inhibitory activity. The enzyme isolated from
Enterobacter cloacae
was found to be the most susceptible. In some cases, the degree of inhibition varied with the time of incubation, and, depending upon the time chosen, widely different observations could be made. It is suggested that, in studies such as these, every consideration should be given to the period of incubation and to the concentration of inhibitor employed. Mixtures of inhibitor and cephaloridine did not always act synergistically against growing bacteria, and a number of reasons for failure are suggested.
Biological Activity of Sch 14342, an Aminoglycoside Antibiotic Coproduced in the Gentamicin Fermentation
Authors: Waitz J. A. , Moss E. L. , Oden E. M. , Wagman G. H. , Weinstein M. J.
Published: June 2012

Sch 14342 is an aminoglycoside antibiotic coproduced as a minor component in the gentamicin fermentation. Sch 14342 was found to have the same antibacterial spectrum as gentamicin in vitro and in vivo, and was approximately one-third as active in mouse protection tests. Sch 14342 relative to gentamicin was one-third as toxic in acute tests in mice, one-eighth as toxic in renal toxicity tests in dogs, and an estimated one-tenth as toxic in cat ataxia tests. Sch 14342 possesses a significantly improved therapeutic index relative to gentamicin with reference to ataxia potential and renal toxicity.
Inhibition of Peptidoglycan Synthesis by the Antibiotic Diumycin A
Authors: Lugtenberg E. J. J. , Hellings J. A. , Van De Berg G. J.
Published: June 2012

Diumycin A, a new antibiotic, was found to inhibit cell wall synthesis by
Staphylococcus aureus
, a phenomenon accompanied by accumulation of uridine-5′-diphosphate-
N
-acetyl-muramyl-pentapeptide. The antibiotic inhibited in vitro peptidoglycan synthesis by particulate preparations of
Bacillus stearothermophilus
and
Escherichia coli
by preventing the utilization of
N
-acetyl-glucosamine-
N
-acetyl-muramyl-pentapeptide. In contrast to vancomycin, the antibiotics diumycin, prasinomycin, moenomycin, 11.837 RP, and enduracidin do not inhibit particulate
d
-alanine carboxypeptidase.
7-Chlorolincomycin Therapy of Pulmonary Infections Due to
Mycoplasma pneumoniae
Authors: Axelrod Judith , Meyers Burt R. , Hirschman Shalom Z.
Published: June 2012

Nine ill patients with serologically proved pulmonary infection due to
Mycoplasma pneumoniae
were treated with 7-chlorolincomycin. The symptomatic responses with 900 to 1,200-mg doses were dramatic.
Lysis of Trypanosoma cruzi by Pseudomonas fluorescens
Authors: Mercado T I , Colón-Whitt A
Published: June 2012

Trypomastigotes of Trypanosoma cruzi isolated from the blood of infected mice were lysed within 24 h by an extracellular substance produced by Pseudomonas fluorescens. Isolation of the anti-trypanosomal factor (ATF) was accomplished by growth of the organisms in a defined medium, extracellular secretion by the sedimented cells, sterilization by filtration, lyophilization, dialysis, and gel filtration. Chromatographic separation with Sephadex G-25 and G-200 disclosed the occurrence of three active fractions. ATF-I(1) exhibited a molecular weight higher than 440,000. ATF-II and ATF-III were considerably smaller (molecular weights approximately 1,355 and 1,060, respectively). The lytic substance contained protein and lipopolysaccharide, was resistant to heat and freezing, was not proteolytic or hemolytic, and was not inhibited by trypsin but was suppressed by pronase.
Cefoperazone pharmacokinetics in preterm infants
Authors: Bosso J A , Chan G M , Matsen J M
Published: June 2012

The elimination pharmacokinetics of cefoperazone, a new cephalosporin, were studied in 15 preterm infants ranging in gestational age from 32 to 36 weeks and in postnatal age from 1 to 6 days. The infants received a single dose of either 50 or 250 mg of cefoperazone per kg by intravenous infusion. Blood samples were collected at specified times after completion of the drug infusion and then assayed for cefoperazone. Pharmacokinetic parameters were determined by noncompartmental analysis. Mean values for plasma half-life, elimination rate constant, apparent steady-state volume of distribution, and total body clearance were 5.53 h, 0.15 h-1, 124 ml/kg, and 36 ml/h per kg, respectively, for the group receiving a 50-mg/kg dose and 5.76 h, 0.14 h-1, 111 ml/kg, and 35 ml/h per kg, respectively, for the group receiving a 250-mg/kg dose. Positive correlations between gestational age and clearance and elimination rate were detected. A 50-mg/kg dose every 12 h ensured adequate serum levels for most of the common neonatal pathogens. Other than a transient rise in eosinophils in four subjects, no adverse effects were noted.
Inhibition of Chlorination in
Streptomyces aureofaciens
by Nitriles and Related Compounds
Authors: Goodman Joseph J. , Matrishin Mary
Published: June 2012

A number of nitriles and cyano compounds inhibited chlorination by
Streptomyces aureofaciens
. In most cases, this inhibition was enhanced by bromide. Methylene blue and
p
-amino-propiophenone reversed the inhibition to some extent.
Microbiological Properties of a New Cephalosporin, BL-S 339: 7-(Phenylacetimidoyl-aminoacetamido)-3-(2-Methyl-1, 3,4-Thiadiazol-5-Ylthiomethyl)Ceph-3-em-4-Carboxylic Acid
Authors: Misiek M. , Pursiano T. A. , Leitner F. , Price K. E.
Published: June 2012

BL-S 339 is a new broad-spectrum, parenterally effective cephalosporin whose expression of antibacterial activity in vitro is markedly affected by the nature of the assay medium. When assayed in nutrient agar, BL-S 339 was more active than cephalothin against strains of
Diplococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, Enterobacter
, and indole-positive
Proteus
sp. However, when assayed in Mueller-Hinton medium, its activity, especially against gram-negative bacteria, was reduced substantially, whereas the activity of cephalothin was virtually unaffected by the assay medium. The in vivo activity of BL-S 339 correlated well with its activity in nutrient agar; when administered subcutaneously to mice, it was therapeutically more efficacious than cephalothin in infections caused by both gram-positive and gram-negative bacteria. When BL-S 339 was administered intramuscularly to mice, the concentrations achieved in the blood were three times those achieved with cephalothin. BL-S 339 was bound to human serum proteins to the same extent as cephalothin. Recovery of BL-S 339 in the urine within the 24-hr period after intramuscular administration to rats was three times that of cephalothin.
Bacteriostatic and Bactericidal Activities of Various Antibiotics Against
Bacteroides fragilis
Authors: Zabransky R. J. , Johnston J. A. , Hauser K. J.
Published: June 2012

The minimal inhibitory concentrations and minimal bactericidal concentrations of seven antibiotics were determined by broth dilution tests for 50 clinical isolates of
Bacteroides fragilis
. Chloramphenicol, erythromycin, lincomycin, clindamycin, and rifampin inhibited 80 to 100% of the strains at concentrations attainable in the serum. Penicillin and tetracycline were less effective, inhibiting 4 and 40% of the strains, respectively, at concentrations attainable in the serum. The strains exhibited a bimodal distribution with tetracycline but a very narrow pattern of susceptibility with chloramphenicol. Bactericidal concentrations were 4- to 128- fold higher than minimal inhibitory concentrations for all antibiotics; only clindamycin showed bactericidal activity at levels attainable in serum. Clindamycin was significantly more effective than lincomycin as determined by tests of inhibitory and bactericidal activity. The distinct patterns of susceptibility of
B. fragilis
may be used for the preliminary selection of antimicrobial therapy.
Studies on the Toxicity and Antiviral Activity of Various Polynucleotides
Authors: Black D. R. , Eckstein F. , DeClercq E. , Merigan T. C.
Published: June 2012

Various polynucleotides were examined for antiviral activity and toxicity in mice. Although the antiviral potency of the various interferon inducers varied, there was a concomitant variation in toxicity. This was reflected by a fivefold range in therapeutic ratio for the various compounds. In addition, no polynucleotide proved to be a more potent interferon inducer than polyinosinic·polycytidylic acid [(poly rI)·(poly rC)]. Our results suggest that there may be intrinsic limitations to the development of polynucleotide interferon inducers having improved therapeutic ratios.
Prophylactic Activity of a Phenanthrene Methanol (WR 33063) and a Quinoline Methanol (WR 30090) in Human Malaria
Authors: Clyde David F. , McCarthy Vincent C. , Rebert Cletus C. , Miller Roger M.
Published: June 2012

WR 33063 (3-bromo-10-[α-hydroxy-β-(
n, n
-diheptylamino)ethyl]-phenanthrene hydrochloride) and WR 30090 (6,8-dichloro-2,3,4-dichlorphenyl-di-
n
-butylaminoethyl-4- quinolinemethanol hydrochloride) were tested for suppressive prophylactic effect on induced malaria in nonimmune volunteers living in an area where malaria is not naturally transmitted. Doses of 800 mg of WR 33063 and 690 or 460 mg of WR 30090 were given at weekly intervals to men exposed on the day of the first dose to mosquitoes heavily infected with chloroquine- and pyrimethamine-resistant strains of
Plasmodium falciparum
. WR 33063 did not interfere with early development of infection, but WR 30090 given for 8 weeks provided suppressive cures in 20 of 26 men.
P. vivax
infections similarly induced broke through WR 30090 treatment in 4 of 15 men, and most of the remainder experienced malaria after completion of the prophylactic course. No side effects of treatment were observed.
Treatment of Falciparum Malaria from Vietnam with a Phenanthrene Methanol (WR 33063) and a Quinoline Methanol (WR 30090)
Authors: Canfield Craig J. , Hall Anthony P. , MacDonald Bruce S. , Neuman David A. , Shaw James A.
Published: June 2012

Two new investigational antimalarial drugs developed by the U.S. Army Malaria Research Program were tested in patients with multi-drug-resistant falciparum malaria from Vietnam. WR 33063, a phenanthrene methanol, cured 13 patients treated in the United States. All of these patients had suffered multiple recrudescences after treatment with standard antimalarial drugs. In addition, 23 of 25 patients with acute attacks of falciparum malaria treated in Vietnam were cured. The rate of clinical response was prompt. WR 30090, a quinoline methanol, similarly cured eight patients with multiple recrudescences in the United States and 23 of 26 patients in Vietnam. Adverse effects associated with the drugs were not seen. These drugs signify a major advance in the chemotherapy of drug-resistant falciparum malaria.
Cephamycins, a New Family of β-Lactam Antibiotics: Antibacterial Activity and Resistance to β-Lactamase Degradation
Authors: Daoust Donald R. , Onishi H. Russell , Wallick Hyman , Hendlin David , Stapley Edward O.
Published: June 2012

The susceptibility to some cephalosporin antibiotics and to cephamycin C, a member of a new family of β-lactam antibiotics, was evaluated for 466 cultures representing 11 different genera or species of gram-negative clinical isolates. The susceptibility of 39 gram-negative cultures known to produce β-lactamase was also determined. The β-lactamase activity of a representative group of the clinical isolates and the 39 enzyme producers was studied with the cephalosporins (cephalothin and cephaloridine) and cephamycin C as substrates and was related to the in vitro disc susceptibility to these same antibiotics. The significant resistance to β-lactamase displayed by the cephamycins is reflected in the kinetics of enzyme activity (
K
m
and
V
max
) that are reported for the cephalosporins and the cephamycins. Resistance to β-lactamase is probably one of the reasons that many cephalosporin-resistant cultures are susceptible to cephamycin C.
Amoxicillin, a New Penicillin Antibiotic
Authors: Handsfield H. Hunter , Clark Hugh , Wallace James F. , Holmes King K. , Turck Marvin
Published: June 2012

Amoxicillin (α-amino-
p
-hydroxybenzyl penicillin, BRL 2333) is a new semisynthetic penicillin which is structurally similar to ampicillin, but which is better absorbed and yields higher concentrations in serum and urine. The in vitro susceptibility of 145 strains of
Enterobacteriaceae
and 30 isolates of
Pseudomonas aeruginosa
was determined against various concentrations of amoxicillin and ampicillin in agar. In addition, inhibitory zones around discs containing 10 μg of amoxicillin were measured and compared with results of agar dilution studies. The drug also was evaluated in the treatment of 38 patients with bacteriuria, who received doses of either 750 mg or 1 g/day for 10 days. In vitro, amoxicillin was comparable in activity to ampicillin; most isolates of
Escherichia coli
and
Proteus mirabilis
were inhibited by 10 μg or less/ml, whereas the majority of strains of
Enterobacter, Klebsiella
, indole-positive
Proteus
species, and
Pseudomonas
grew in concentrations greater than 50 μg/ml. Clinically, amoxicillin was effective in eradicating bacteriuria due to susceptible organisms and was very well tolerated. For practical purposes, however, amoxicillin performed no better than a host of other drugs presently available for the treatment of acute, uncomplicated bacteriuria.
Exocellular β-Lactamases of
Streptomyces albus
G and Strains R39 and K11
Authors: Johnson Kenneth , Dusart Jean , Campbell James N. , Ghuysen Jean-Marie
Published: June 2012

The β-lactamases excreted by the highly benzylpenicillin-susceptible
Streptomyces
strain R39 and the highly benzylpenicillin-resistant
Streptomyces albus
G were isolated and purified. Neither β-lactamase exhibited
dd
-carboxypeptidase activity. Both were anionic at
p
H 8.3, did not require metal ions, and were not sensitive to iodine, but were inhibited by Cu
2+
and readily inactivated by heat.
p
-Chloromercuribenzoate, iodoacetate,
p
-aminobenzoate, and substrates and inhibitors of
dd
-carboxypeptidase had no effect on β-lactamase activity. The
K
m
and
V
max
values for β-lactamase activity were studied with 6-aminopenicillanic acid and with various penicillins and cephalosporins. The β-lactamase from the related strain K11 of
Streptomyces
, which is intermediate in its susceptibility to benzylpenicillin, was partially purified, and its activity was compared on the various substrates.
Comparison of Five Aminocyclitol Antibiotics In Vitro Against
Enterobacteriaceae
and
Pseudomonas
Authors: Karney Walter , Holmes King K. , Turck Marvin
Published: June 2012

The in vitro susceptibility of 163 strains of
Enterobacteriaceae
and 23 isolates of
Pseudomonas aeruginosa
to various concentrations of gentamicin, kanamycin, spectinomycin, tobramycin, and BB-K8, a new semisynthetic aminoglycoside antibiotic, was determined. Studies were performed in Mueller-Hinton agar and broth, and two different sizes of bacterial inocula were used. On a weight basis, gentamicin and tobramycin demonstrated comparable activity in vitro and were the most active of the five drugs tested against
Escherichia coli, Klebsiella, Enterobacter
, and
Proteus
species. All of these organisms were inhibited by gentamicin or tobramycin at concentrations of 5.0 μg or less/ml in agar with both inocula of bacterial cells. In addition, tobramycin was the most active drug against isolates of
P. aeruginosa
and gentamicin was the most active against
Salmonella
and
Shigella
species. Although kanamycin and BB-K8 demonstrated a high degree of activity against most
Enterobacteriaceae
, they were not the most active agents tested for any genus. Spectinomycin was the least active compound, and many isolates grew in concentrations higher than those readily attainable in serum.
Modified Broth-Disk Method for Testing the Antibiotic Susceptibility of Anaerobic Bacteria
Authors: Wilkins Tracy D. , Thiel Teresa
Published: June 2012

The most commonly used method for testing the antibiotic susceptibility of aerobic and facultative bacteria is the disk diffusion method. However, some anaerobic bacteria do not grow well enough in anaerobic jars for performance of disk diffusion tests. A modification of the broth-disk method of Schneierson allowed us to determine antibiotic susceptibility in a completely anaerobic environment. Commercial antibiotic disks were added anaerobically to tubes of prereduced brain heart infusion broth to achieve a concentration of each antibiotic approximating that attainable in blood. The tubes were then inoculated and incubated for 18 h. Resistance or susceptibility to each antibiotic was determined according to the amount of growth in each tube as compared with a control culture without the antibiotic. There was good correlation between results obtained by this broth-disk method and minimal inhibitory concentrations.
Mode of Action of Illudin S
Authors: Walser J. , Heinstein P. F.
Published: June 2012

The effect of the antitumor antibiotic illudin S on bacterial macromolecular synthesis was investigated. Illudin S was found to be inhibitory to in vivo deoxyribonucleic acid (DNA) synthesis from thymidine. Ribonucleic acid (RNA) synthesis was inhibited only at a concentration of illudin S 10 times that which inhibited DNA synthesis. The rate of protein synthesis remained the same except for a brief initial inhibition. When thymidine triphosphate was used for in vitro DNA synthesis, inhibition by illudin S did not occur, as tested with partially purified DNA polymerase II from
Escherichia coli pol A
1
−
, with
E. coli
DNA-dependent RNA polymerase, with
E. coli pol A
1
−
spheroplasts, and with frozen and thawed
Bacillus subtilis
cells. A protein fraction isolated from
B. subtilis
capable of forming thymidine mono-, di-, and triphosphates from thymidine was not inhibited by illudin S. Furthermore,
14
C-illudin S taken up by
B. subtilis
cells was reisolated unchanged, making an intracellular activation of illudin S unlikely. Therefore, an attractive hypothesis is that illudin S inhibits DNA synthesis from thymidine which does not proceed through deoxyribonucleoside triphosphates, the generally accepted substrates for DNA synthesis.
Relationships Between Curing of the F Episome by Rifampin and by Acridine Orange in
Escherichia coli
Authors: Riva S. , Fietta A. , Berti M. , Silvestri L. G. , Romero E.
Published: June 2012

Subinhibitory doses of rifampin cured F
+
Escherichia coli
cells from the episome. The target of the drug was transcription because
E. coli
mutants with a ribonucleic acid polymerase resistant to rifampin were not cured. The experimental conditions required for optimal curing with rifampin very closely resembled those required for curing with acridine orange. Mutants were found which are more resistant to curing by both acridine orange and rifampin. Probably the two drugs affect a common metabolic step, or alternatively they may inhibit the synthesis of a factor which is necessary for the replication of the episome.
Pharmacokinetics of the Aminoglycoside Antibiotic Tobramycin in Humans
Authors: Naber Kurt G. , Westenfelder Silvia R. , Madsen Paul O.
Published: June 2012

The pharmacokinetics, distribution, and plasma and renal clearance of a new aminoglycoside antibiotic, tobramycin, was studied in the treatment of 18 elderly male patients (average age, 69 years) with urinary tract infections. Ten of these patients had normal renal function and eight had impaired renal function of various degrees. After administration of 1 mg of tobramycin/kg of body weight every 6 to 8 h (two to three times the half-life), urine concentrations were found to be sufficient in the treatment of urinary tract infections caused by susceptible organisms. The renal clearance of tobramycin during constant intravenous infusion was also studied in eight patients. Good correlation was found between the patients serum creatinine and the half-life of tobramycin. The half-life of tobramycin in patients with normal renal function (serum creatine [Formula: see text] to 1.5 mg/100) was on the average 3 h. For practical purposes, therefore, the dosage of tobramycin in the treatment of urinary tract infections should be 1 mg/kg of body weight every 6 to 8 h in patients with normal renal function. For patients with impaired renal function, the dosage interval is calculated by multiplying the patients' serum creatinine by six. If the dosage intervals are kept unchanged, the dosage must be divided by the patients' serum creatinine. The initial loading dose should always be 1 mg/kg. The total renal clearance of tobramycin (92% of the glomerular filtration rate) was not influenced by the administration of probenecid, which indicates that tobramycin is excreted only by glomerular filtration.
Defective Transamination, a Mechanism for Resistance to Ketomycin in
Escherichia coli
Authors: Jackson Julius H. , Umbarger H. E.
Published: June 2012

A spontaneous mutant of a derivative of
Escherichia coli
strain K-12 resistant to 50 μg of ketomycin per ml was selected. The mutant displayed a two- to threefold derepression of the isoleucine-valine biosynthetic enzymes and a reduced growth rate in minimal medium. The lesion was found to lie in the gene (
ilvE
) specifying transaminase B and resulted in an isoleucine limitation. The presence of exogenous isoleucine during growth in minimal medium restored normal phenotypic properties. The reduced transaminase B activity is responsible for the resistance to ketomycin. An unusual derepression of the acetohydroxy acid synthetase in response to an isoleucine limitation was noted.
Suppression by 1-β-
d
-Ribofuranosyl-1,2,4-Triazole-3-Carboxamide (Virazole, ICN 1229) of Influenza Virus-Induced Infections in Mice
Authors: Khare Gyaneshwar P. , Sidwell Robert W. , Witkowski J. T. , Simon Lionel N. , Robins Roland K.
Published: June 2012

1-β-
d
-Ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole) was found to possess significant antiviral activity against aerosol-induced or intranasally induced influenza A
0
, A
2
, and B virus infections in mice. Significant protection was achieved by both oral and intraperitoneal routes of administration. Depending upon the level of virus infection, antiviral activity was best observed at the daily dose of 75 mg/kg. The efficacy of the compound was evidenced by an increase in survivor number, prolongation of mean survival time, suppression of lung consolidation, or decrease in hemagglutinin titer in the infected lung samples. The therapeutic value of this synthetic triazole nucleoside was evident as noted by a significant increase in survivor number even if the treatment was started as late as 24 h after infection with an aerosol of influenza A
2
virus.
Distribution and Blood-to-Milk Transfer of Labeled Antibiotics
Authors: Ziv Gideon , Bogin Eitan , Shani (Mishkinsky) Jashovam , Sulman Felix Gad
Published: June 2012

Radioactivity distribution was determined in serum and milk of lactating ewes after parenteral administration of five labeled antibiotics:
14
C-benzylpenicillin G,
3
H-dihydrostreptomycin,
3
H-tetracycline,
14
C-chloramphenicol, and
14
C-spiramycin. Antibiotic levels were measured simultaneously by microbiological assay. Radiochemical and microbiological assay procedures presented similar kinetic patterns for uptake in serum and penetration into milk, except for tetracycline. Small reductions in milk pH markedly increased the excretion of spiramycin and slightly influenced the milk passage of penicillin, dihydrostreptomycin, and tetracycline but did not alter the transfer of chloramphenicol into milk. Thus, it appears that the five antibiotics penetrate milk in accordance with the nonionic passive diffusion principle, and that good agreement is achieved between the calculated and observed milk/serum ultrafiltrate concentration ratios obtained during equilibrium.
Pharmacokinetic Studies in Animals and Humans of a New Cephalosporin, the Sodium Salt of 7-Cyanacetamidocephalosporanic Acid
Authors: Luscombe D. K. , Nicholls P. J. , Owens D. R. , Russell A. D.
Published: June 2012

The sodium salt of 7-cyanacetamidocephalosporanic acid (CAA) had a relatively short serum half-life in rabbits (21 min by intravenous and 30 min by intramuscular administration) and in humans (33 min by intravenous injection). The drug was not extensively bound (about 35%) to serum in either species. Even after large doses (500 mg/kg), CAA was not well absorbed from the gastrointestinal tract of rabbits. Urinary excretion of antibacterial activity was rapid after intravenous and intramuscular administration in rabbits and after intravenous administration in men. Expressed as unchanged CAA, antibacterial activity appeared in the urine to the extent of 84% for humans, 35% for rabbits and 32% for rats. Excretion proceeded partly by active renal tubular secretion in rabbits. In this latter species, low concentrations of the active drug were detected in cerebrospinal fluid and bile after an intravenous dose of 25 mg/kg. CAA was well tolerated after intravenous administration of a single dose in both rabbits and humans.
Penetration of clindamycin, cefoxitin, and metronidazole into pelvic peritoneal fluid of women undergoing diagnostic laparoscopy
Authors: Berger S A , Kupferminc M , Lessing J B , Gorea A , Gull I , Peyser M R
Published: June 2012

A single dose of clindamycin, cefoxitin, or metronidazole was administered to each of 30 women. The mean concentration of cefoxitin in pelvic fluid at 1 h exceeded those of the other two drugs (P less than 0.007). Cefoxitin concentrations were inferior to those of the other drugs when compared with the published MIC for 90% of Bacteroides fragilis strains.
Lividomycin Resistance in Staphylococci by Enzymatic Phosphorylation
Authors: Kobayashi Fujio , Koshi Tomoyuki , Eda Junji , Yoshimura Yoko , Mitsuhashi Susumu
Published: June 2012

Enzymatic inactivation of lividomycin (LV) was attempted with nine clinical isolates of staphylococci including LV-susceptible and -resistant strains. LV inactivation and the incorporation into LV of
32
P from γ-
32
P-adenosine triphosphate were demonstrated in the presence of cell-free extracts from LV-resistant strains but not from LV-susceptible ones. The enzyme was purified approximately 82-fold from a resistant
Staphylococcus aureus
strain by means of ammonium sulfate fractionation and column chromatography. Some properties of the partially purified LV-phosphorylating enzyme were quite similar to those of an enzyme from
Escherichia coli
carrying an R factor conferring LV resistance, and the phosphorylated product of the drug was also found to be identical with that produced by
E. coli
carrying an R factor, i.e., 5″-phosphoryl-LV.
Clinical Pharmacology of Ticarcillin (α-Carboxyl-3-Thienylmethyl Penicillin, BRL-2288)
Authors: Rodriguez Victorio , Inagaki Jiro , Bodey Gerald P.
Published: June 2012

Clinical pharmacological studies of ticarcillin (α-carboxyl-3-thienylmethyl penicillin, BRL-2288) were conducted in patients with metastatic cancer and leukemia.After administration of 0.5 g intramuscularly, 1 g intramuscularly, and 1 g intravenously, the mean peak concentrations in serum were 18, 35, and 106 μg/ml, respectively. Greater than 80% of ticarcillin was excreted in the urine during the subsequent 6-h period. The mean concentrations in the serum of patients 15 min after they received an intravenous injection of 4 g of ticarcillin with and without probenecid were 508 and 519 μg/ml, respectively. Serum levels were determined in patients who received ticarcillin for therapy of infection in doses of 5 g every 6 h. The mean drug concentration in serum 15 min after the rapid administration of the first dose was 433 μg/ml. Subsequent doses were given during a 2-h infusion and the study was repeated 2 days later. The average initial serum level (4 h after the completion of the preceding dose) was 19 μg/ml, and the mean serum level at 15 min was 213 μg/ml. Drug concentrations in the serum of patients receiving ticarcillin by infusion in doses of 3.5 g every 4 h were also determined. In patients with normal renal function, the average initial serum level (2 h after completion of the preceding dose) was 49 μg/ml and the mean level at 15 min was 210 μg/ml. Drug concentrations in the serum of patients with impaired renal function were considerably higher. No detectable levels of ticarcillin were found in the cerebrospinal fluid.
Antibiograms and Lipid Contents of Pigmented and Nonpigmented Strains of
Serratia marcescens
Authors: Miller Marcia A. , Chang Chuan-Yi , Tsang Joseph C.
Published: June 2012

The antibiogram of pigmented 08 and nonpigmented Bizio strains of
Serratia marcescens
was determined. Their lipid content was also analyzed.
Comparative In Vitro Activity of Three Aminoglycosidic Antibiotics: BB-K8, Kanamycin, and Gentamicin
Authors: Yu Pauline K. W. , Washington John. A.
Published: June 2012

Kanamycin, BB-K8, and gentamicin were tested in parallel against 1,037 bacterial strains isolated from clinical material. The activity of BB-K8 at 20 μg/ml was comparable to that of gentamicin at 8 μg/ml against
Pseudomonas aeruginosa
and against
Enterobacteriaceae
, with the exception of gentamicin-resistant strains of
Proteus rettgeri
and
Providencia stuartii
, in which case the activities of BB-K8 and kanamycin were the same. BB-K8 exhibited little or no activity against streptococci. The activity of BB-K8 was affected by pH and inoculum size. A regression graph for inhibition data with a 10-μg disk of BB-K8 was developed, and synergistic activity of penicillin and BB-K8 against
Streptococcus faecalis
was tested.
Maridomycin, a New Macrolide Antibiotic. In Vitro Antibacterial Activity of 9-Propionylmaridomycin
Authors: Kondo Masahiro , Oishi Tokiko , Tsuchiya Kanji , Goto Sachiko , Kuwahara Shogo
Published: June 2012

9-Propionylmaridomycin shows in vitro antibacterial activity against gram-positive bacteria and has some action on
Neisseria gonorrhoeae
and
Vibrio cholerae
, but is generally inactive against many gram-negative rods. This antibiotic exhibits strong activity against clinical isolates of
Staphylococcus aureus
which are highly resistant to erythromycin or oleandomycin, or both, but which are sensitive to josamycin and kitasamycin. Strains resistant to josamycin and kitasamycin were also found to be resistant to this antibiotic. A significant feature of 9-propionylmaridomycin is a lack in its ability to induce resistance induction in resistance-inducible strains of staphylococci to erythromycin. Several antibacterial features of 9-propionylmaridomycin such as the influence of medium pH, inoculum size, effect of addition of horse serum, development of resistance, cross resistance, and bacteriostatic activity were shown to be almost identical to those of josamycin and kitasamycin. The antibacterial activity of 9-propionylmaridomycin was stable in solutions at pH levels of 4, 7, and 9.
Enumeration of Tubercle Bacilli in Sputum of Patients with Pulmonary Tuberculosis
Authors: Hobby Gladys L. , Holman Audrey P. , Iseman Michael D. , Jones Julia M.
Published: June 2012

A method for precise microscopic enumeration of acid-fast bacilli in the sputum of patients with pulmonary tuberculosis is described. The total number of acid-fast bacilli and the number of culturable cell units of tubercle bacilli per milliliter of sputum were determined in 269 specimens from 28 patients collected prior to and/or during chemotherapy, to establish the usefulness of the procedure for evaluation of the effects of chemotherapy. Prior to or very early in the course of therapy, there was good agreement between microscopically and culturally measurable bacilli in 27 of 28 patients. Thereafter, there were systematic divergences in five patients and occasional divergences in most others. Yet, in general, in 20 of the 28 patients, the microscopically determined population provided a useful measure of the number of culturable tubercle bacilli present. Although the microscopic procedure does not allow species identification of mycobacteria or differentiation between viable and nonviable cells, it often provided, within hours rather than days or weeks, useful information on the residual burden of acid-fast bacilli in sputum during chemotherapy. The nature of the disease in those patients in whom microscopy failed to provide useful information is discussed.
Additional Antibiotic Inhibitors of Peptidoglycan Synthesis
Authors: Linnett Paul E. , Strominger Jack L.
Published: June 2012

Diumycin, janiemycin, nisin, and subtilin inhibited peptidoglycan synthesis catalyzed by particulate enzyme systems from
Bacillus stearothermophilus
and
Escherichia coli
. All of these, except for nisin, also induced accumulation of the lipid intermediate in peptidoglycan synthesis. Concentrations required for 50% inhibition of peptidoglycan synthesis were less than 0.1 μg/ml for diumycin and in the range of 10 to 100 μg/ml for janiemycin, nisin, and subtilin in both organisms. The discrepancy between the extremely low concentration of diumycin required to inhibit the in vitro system from
E. coli
and the much higher concentration required to inhibit growth of the organism is noteworthy.
Sulfonamide Resistance of Propionibacteria: Nutrition and Transport
Authors: Reddy M. S. , Williams F. D. , Reinbold G. W.
Published: June 2012

Three variations of a synthetic growth medium were used to study the folic acid and
p
-aminobenzoic acid (PABA) requirements of
Propionibacterium. P. shermanii, P. freudenreichii, P. thoenii
, and
P. arabinosum
synthesize folic acid and do not require PABA or folic acid.
P. pentosaceum, P. jensenii
, and
P. rubrum
are stimulated by folic acid or PABA, but do not show an absolute requirement.
P. peterssonii
shows a requirement for either PABA or folic acid. The addition of 300 μg of sulfadiazine per ml did not inhibit growth of propionibacteria in the synthetic medium, synthetic medium plus PABA, or synthetic medium plus folic acid.
P. freudenreichii
was not inhibited even when 500 μg of sulfadiazine per ml was added to the synthetic medium, nor did it degrade sulfadiazine significantly. Trimethoprim totally inhibited the growth of
Propionibacterium
. Radioactive sulfadiazine was transported by sulfadiazine-sensitive
Escherichia coli
but not by
P. freudenreichii
, indicating that the sulfadiazine resistance of propionibacteria could be mainly due to their inability to transport sulfonamides.
Selective Membrane Toxicity of the Polyene Antibiotics: Studies on Lecithin Membrane Models (Liposomes)
Authors: Hsuchen Chuen-Chin , Feingold David S.
Published: June 2012

In the absence of sterol, amphotericin B at 5 × 10
−6
M caused maximum marker release from the saturated dipalmitoyl lecithin liposomes, minimum release from the unsaturated dioleoyl lecithin liposomes, and an in-between response from egg lecithin liposomes. Nystatin at 2.5 to 4.0 × 10
−5
M induced appreciable marker release from all three types of sterol-free liposomes. The amphotericin B- and nystatin-induced permeability changes in dipalmitoyl lecithin liposomes were drastically suppressed by the incorporation of cholesterol or stigmasterol (with identical Δ5 sterol nuclei), but were unaffected by the incorporation of ergosterol or 5,7-cholestadien-3β-ol (with identical Δ5,7 sterol nuclei). The nystatin sensitivity of dioleoyl lecithin liposomes remained low after the incorporation of cholesterol or stigmasterol, but was greatly enhanced by the incorporation of ergosterol or 5,7-cholestadien-3β-ol. Digitonin, a compound known to interact specifically with membrane sterol, induced marker release from liposomes in proportion to the amount of either cholesterol or ergosterol incorporated; epicholesterol did not sensitize to digitonin. These results lead to the following conclusions: (i) polyene-induced permeability alteration in model membrane systems is effected by the composition of membrane phospholipid fatty acyl chains; (ii) the distribution of double bonds in the sterol nucleus is related to the selective toxicity of the polyenes toward natural sterol-containing membranes; and (iii) polyenes differ in membrane selectivity.
Selective Membrane Toxicity of the Polyene Antibiotics: Studies on Natural Membranes
Authors: Hsuchen Chuen-Chin , Feingold David S.
Published: June 2012

The effect of polyene antibiotics on
Candida albicans
, human erythrocytes, and
Acholeplasma laidlawii
was studied. The results sustain the observations made with lecithin-sterol liposomes. The distribution of double bonds in the membrane sterol nucleus appears to be of major importance in conferring polyene susceptibility; those sterols with the ergosterol nucleus are far more effective than those with a nucleus similar to cholesterol. Different polyenes vary in their membrane selectivity. The clinical implications of these observations are discussed.
In Vitro Activity of Ampicillin or Vancomycin Combined with Gentamicin or Streptomycin Against Enterococci
Authors: Harwick Herbert J. , Kalmanson George M. , Guze Lucien B.
Published: June 2012

Minimum inhibitory and bactericidal concentrations of four antibiotics and their combinations were determined for 38 strains of enterococci by a microtitration tube dilution technique. The drugs were ampicillin, vancomycin, gentamicin, and streptomycin; the combinations were ampicillin-gentamicin, ampicillin-streptomycin, vancomycin-gentamicin, and vancomycin-streptomycin. At achievable serum concentrations, ampicillin alone killed 60% of strains, whereas combination with streptomycin increased this to 90% and with gentamicin to 100%. Vancomycin alone showed striking inhibitory activity, but very poor bactericidal activity at achievable concentrations. Combination with one of the aminoglycosides increased the bactericidal activity substantially. When combined with ampicillin, gentamicin was both more active and showed synergistic bactericidal activity significantly more often (
P
< 0.01) than streptomycin.
Ticarcillin Therapy of Infections
Authors: Rodriguez Victorio , Bodey Gerald P. , Horikoshi Noboru , Inagaki Jiro , McCredie Kenneth B.
Published: June 2012

Ticarcillin was administered as initial therapy during 73 episodes of infections occurring in 69 adults with neoplastic diseases. During the first six infections, doses of 5 gm were dissolved in 200 ml of solvent and administered intravenously over a 2-h period every 6 h. Four of six infections responded to therapy. However, two of the five
Pseudomonas
infections failed to respond, whereas the organisms causing the infection were sensitive to ticarcillin in vitro. During the remaining 67 infections, doses of 3.5 g were similarly dissolved and administered intravenously over a 2-h period every 4 h. The overall response to ticarcillin in these 67 infections was 43%. However, 18 of 20
Pseudomonas
infections, three
Proteus
spp. infections, and one infection caused by
H. influenzae
responded. Only 1 of 7 infections caused by mixed organisms and 5 of 13 infections in which the etiologic agent could not be identified responded. Ticarcillin was ineffective against the majority of
Escherichia coli
and
Klebsiella
spp. infections, organisms which were resistant to ticarcillin in vitro. The majority of patients were neutropenic, but the response rate was not dependent on the number of circulating polymorphonuclear neutrophilic leukocytes. Superinfection occurred in seven patients. Erythematous skin rash occurred in two patients, which subsided after discontinuation of the drug. No liver or renal toxicity occurred that could be attributed to ticarcillin.
Activity of Five Aminoglycoside Antibiotics In Vitro Against Gram-Negative Bacilli and
Staphylococcus aureus
Authors: Young Lowell S. , Hewitt William L.
Published: June 2012

The in vitro susceptibility to BB-K8, butirosin, gentamicin, sisomicin, and tobramycin of seven groups of clinically significant gram-negative bacilli and
Staphylococcus aureus
was assessed by using the International Collaborative Study-World Health Organization criteria. The activity of gentamicin, sisomicin, and tobramycin generally paralleled each other. Sisomicin was the most potent compound by weight and usually demonstrated the most rapid rate of killing. BB-K8 and butirosin were less potent, but higher serum levels may be achieved with these agents. BB-K8 generally showed the greatest ratio between achieveable mean peak serum levels and concentrations needed to inhibit [Formula: see text] of each group of organisms tested. Additionally, BB-K8 was active against six of seven highly gentamicin-resistant strains. All of these antibiotics showed diminished activity at pH 6.4 but only gentamicin and sisomicin showed occasionally enhanced activity at pH 8.4.