bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Characterization of the R Factors Implicated in the Carbenicillin Resistance of a Sequence of
Pseudomonas aeruginosa
Strains Isolated from Burns
Authors: Ingram Lewis C. , Richmond M. H. , Sykes R. B.
Published: June 2012

An outbreak of R-factor-mediated carbenicillin resistance in
Pseudomonas aeruginosa
in burned patients in March 1969 was followed by a second outbreak 6 months later. No R-factor-carrying
P. aeruginosa
strains were detected in the intervening period but R-factor-determined lactamase was commonly encountered, particularly in
Klebsiella aerogenes
strains. A comparison of the molecular properties of the R factors in pseudomonads from the first and second phases with those in the
Klebsiella
strains from the intervening period showed them to be very closely related. A single R-factor type therefore may have been maintained in the Burns Unit between the two
Pseudomonas
outbreaks as a plasmid conferring resistance to ampicillin in
K. aerogenes
.
Reversible Inhibition of Herpes Simplex Virus Replication by Hydroxyurea
Authors: Rosenkranz Herbert S. , Becker Yechiel
Published: June 2012

Hydroxyurea, at a concentration of 5 × 10
−2
M, inhibits the replication of herpes simplex deoxyribonucleic acid (DNA) in the nuclei of infected cells. As a result, the synthesis of infectious virus progeny was prevented. The presence of parental viral DNA genomes in inhibited cells led to the synthesis of the viral structural peptides. The inhibitory effect of hydroxyurea was reversible; after washing the cells free from hydroxyurea, virus progeny appeared after a lag of 3 h. Upon resumption of viral DNA replication, the content of radioactive viral structural peptides gradually increased in parallel with the increase in mature virions. It is concluded that the information for the synthesis of viral structural peptides is transcribed from the parental DNA genomes.
Susceptibility of Whole Cells and Spheroplasts of
Pseudomonas aeruginosa
to Actinomycin D
Authors: Cheng K.-J. , Costerton J. W. , Singh A. P. , Ingram J. M. , Idziak E. S.
Published: June 2012

Cells of
Pseudomonas aeruginosa
suspended in 0.2 M Mg
2+
, 20% sucrose, 0.01 M tris(hydroxymethyl)aminomethane, or water partially release lipopolysaccharide. The release of alkaline phosphatase from the periplasmic space and the ability to form spheroplasts on lysozyme treatment is directly related to the lipopolysaccharide released during treatment with 0.2 M Mg
2+
, 20% sucrose, or other agents. The synthesis of ribonucleic acid (RNA) by intact cells, magnesium-lysozyme spheroplasts, or 20% sucrose-lysozyme spheroplasts is not sensitive to actinomycin D, whereas RNA synthesis by intact cells or spheroplasts in the presence of ethylene-diaminetetraacetic acid (EDTA) is sensitive to actinomycin D. EDTA alone has an inhibitory effect on RNA synthesis by whole cell, by magnesium-lysozyme spheroplasts, and by 20% sucrose-lysozyme spheroplasts. The experimental data indicate that, although the cell wall is damaged by 0.2 M Mg
2+
or 20% sucrose treatment in the presence of lysozyme, the treated cells or spheroplasts are still resistant to actinomycin D. These results suggest that the cytoplasmic membrane should be considered as the final and determinative barrier to this antibiotic in this organism.
U-42, 126, a New Antimetabolite Antibiotic: Production, Biological Activity, and Taxonomy of the Producing Microorganism
Authors: Haňka L. J. , Dietz A.
Published: June 2012

A new antimetabolite antibiotic, U-42,126, was discovered by use of a specific in vitro screen. U-42,126 was produced by the fermentation of
Streptomyces sviceus
. Its antimicrobial activity in vitro was limited to fungi. Certain bacteria were inhibited only when cultivated in completely synthetic media. U-42,126 was active in vivo against L1210 leukemia in mice.
Penicillin-Tobramycin Synergism Against Enterococci: a Comparison with Penicillin and Gentamicin
Authors: Moellering Robert C. , Wennersten Christine , Weinstein Allan J.
Published: June 2012

Combinations of penicillin plus tobramycin have been compared with penicillin plus gentamicin against 27 strains of enterococci isolated from blood cultures. Penicillin plus gentamicin was synergistic against all strains. The combination of penicillin plus tobramycin was equally effective against strains of
Streptococcus facalis
, but was ineffective against all four strains of
S. faecium
tested.
Miracil D: Inhibition of Deoxyribonucleic Acid Polymerase-Deficient
Escherichia coli
Authors: Rosenkranz Herbert S.
Published: June 2012

Miracil D preferentially inhibited the growth of a deoxyribonucleic acid (DNA) polymerase-deficient
Escherichia coli
strain. This is taken to indicate that miracil D is capable of altering the DNA of living cells and that it may thereby be a potential mutagen and carcinogen.
Interbacterial Transfer of R Factor in Humans
Authors: Neu Harold C. , Huber Philip J. , Winshell Elaine B.
Published: June 2012

In vivo interbacterial transfer of R factor was observed in two patients. Resistance to ampicillin, tetracycline, streptomycin, and chloramphenicol was transferred from
Escherichia coli
in the intestine of a patient with shigellosis to a
Shigella sonnei
strain. In a second patient with partial ureteral obstruction, a resistant
E. coli
strain transferred ampicillin, tetracycline, and streptomycin resistance to a
Proteus mirabilis
strain.
Inhibition of Lipid Synthesis in
Escherichia coli
Cells by the Antibiotic Cerulenin
Authors: Goldberg Israel , Walker James R. , Bloch Konrad
Published: June 2012

The antibiotic cerulenin markedly inhibits the growth of
Escherichia coli
. The effects of the antibiotic on cellular syntheses were studied by measuring the incorporation of labeled precursors into lipids and macromolecules. During the first 40 min after the addition of cerulenin to a culture of growing cells, lipid synthesis was inhibited more than 90% and ribonucleic acid and deoxyribonucleic acid synthesis about 25%, whereas protein synthesis was not affected. At later periods after cerulenin addition (1 to 2 h), the inhibition of cell growth and of lipid and protein synthesis was complete. Upon removal of cerulenin from the culture, growth was restored and lipid synthesis resumed more rapidly than did the synthesis of protein.

Addition of both palmitate and oleate, but not of either fatty acid alone, reversed the inhibition of growth by cerulenin. These findings support the conclusion that the antibiotic effects of cerulenin are due to a specific inhibition of fatty acid synthesis.
Double-Stranded Ribonucleic Acid from Mengo Virus: Production, Characterization, and Interferon-Inducing and Antiviral Activities in Comparison with Polyriboinosinic · Polyribocytidylic Acid
Authors: Falcoff E. , Falcoff R. , Cherby J. , Florent J. , Lunel J. , Ninet L. , De Ratuld Y. , Tissier R. , Vuillemin B. , Werner G. H.
Published: June 2012

Mengo virus double-stranded ribonucleic acid (dsRNA) was obtained on a semi-industrial scale from infected cultures of BHK-21 cells grown in suspension. Yield of the extraction and purification operations was small (about 22 mg from 10
11
cells in a 100-liter culture). Physicochemical characterization of this dsRNA gave an estimated molecular weight close to 4 × 10
6
, a density of 1.59 (similar to that of the poliovirus dsRNA), and a thermal transition midpoint of 94 C. This product was a little more toxic for the mouse, by the intravenous route, than polyriboinosinic · polyribocytidylic acid (poly I:C) and strictly comparable in this respect to poliovirus dsRNA. The interferon-inducing capacity in the mouse and the antiviral activities in the mouse (infected with encephalomyocarditis, Semliki Forest, influenza, foot-and-mouth disease, and murine hepatitis viruses) and in the rabbit (Shope fibroma virus) of the ultraviolet light-inactivated product were practically identical, on a quantitative basis, with those of poly I:C. In vitro and in vivo experiments showed the dsRNA from Mengo virus to be slightly but significantly more resistant than poly I:C to the inactivating effect of human serum.
Mode of Action of Thiolutin, an Inhibitor of Macromolecular Synthesis in
Saccharomyces cerevisiae
Authors: Jimenez A. , Tipper D. J. , Davies J.
Published: June 2012

The sulfur-containing antibiotic thiolutin has been shown to be a potent, reversible inhibitor of the growth of
Saccharomyces cerevisiae
. Viability was unaffected over the concentration range of 4 to 100 μg/ml. At concentrations as low as 2 μg/ml, the drug inhibited ribonucleic acid (RNA) and protein synthesis in whole cells and spheroplasts. At these low concentrations, protein synthesis continued for a short period of time after RNA synthesis was completely stopped. With higher drug concentrations (greater than 20 μg/ml) protein synthesis was inhibited; concentrations of thiolutin up to 100 μg/ml did not affect translocation or peptide bond formation in cell-free protein-synthesizing systems from yeast. The effect of thiolutin on the activity of partially purified deoxyribonucleic acid-dependent RNA polymerases was examined, and the drug was found to be a potent inhibitor of RNA synthesis in vitro. Inhibition was greatest when the polymerase was preincubated with thiolutin. Several mechanisms are discussed to explain the multiple effects of thiolutin on
S. cerevisiae
. Since the action of the drug is easily reversed, thiolutin may prove to be of use in studies of various stages of yeast growth.
Effects of Temperature and of Fatty Acid Substitutions on Colicin K Action
Authors: Plate C. A.
Published: June 2012

The temperature dependence of an early phase of colicin K action was studied. At temperatures of 10 C or lower, colicin K adsorbed to
Escherichia coli
cells, but its ability to cause physiological damage was greatly diminished. Cells treated with colicin K at 10 C exhibited nearly normal levels of β-galactoside accumulation for that temperature, whereas a similar treatment at 27 C strongly reduced the levels of accumulation. Low temperatures also protracted the period during which viability could be restored to a colicin K-treated cell by a treatment with trypsin. Arrhenius plots for the progression of colicin K-treated
E. coli
cells from a trypsin-rescuable to an irrescuable state were biphasic in nature, with an increase in apparent activation energy occurring at temperatures below 21 C. Similar studies carried out with an
E. coli
unsaturated fatty acid auxotroph grown on structurally diverse unsaturated fatty acids revealed that the temperature profile for this phase of colicin K action is influenced by the fatty acid composition of the membrane phospholipids. The results are consistent with the interpretation that the action of colicin K on
E. coli
cells is sensitive to changes in the fluid properties of the membrane.
Effect of Oral Tetracycline on the Occurrence of Tetracycline-Resistant Strains of
Escherichia coli
in the Intestinal Tract of Humans
Authors: Hirsh Dwight C. , Burton Glenna C. , Blenden Donald C.
Published: June 2012

Serial samples of feces from normal human subjects were analyzed for tetracycline-resistant strains of
Escherichia coli
. Subjects were found to be excreting tetracycline-resistant strains in amounts fluctuating with time. Ingestion of tetracycline increased both the number of individuals excreting tetracycline-resistant strains of
E. coli
and the proportion of the total
E. coli
isolates resistant to the antibiotic.
Mechanism of Synergistic Effects of β-Lactam Antibiotic Combinations on Gram-Negative Bacilli
Authors: Farrar W. Edmund , Newsome Jane K.
Published: June 2012

These studies were undertaken to elucidate further the mechanism of synergism of pairs of β-lactam antibiotics on β-lactamase-producing gram-negative bacilli. Three strains of gram-negative bacilli which elaborate β-lactamase enzymes with widely differing properties were employed. The antibacterial effects of β-lactam antibiotics, singly and in combination, on the three organisms investigated were exactly those which would have been predicted on the basis of the enzymological properties of the β-lactamases elaborated by these organisms. The findings thus support the hypothesis that the synergistic antibacterial effects of combinations of β-lactam antibiotics on these organisms were due to inhibition of the enzyme by one of the agents and killing of the organism by the other, which was protected from enzymatic hydrolysis, rather than the alternative possibility that the synergistic effects were due simply to the combined antibacterial actions of the two drugs.
Reconstitution of Colicin E
2
-Induced Deoxyribonucleic Acid Degradation in Spheroplast Preparations
Authors: Almendinger R. , Hager L. P.
Published: June 2012

Spheroplasts are insensitive to colicin E
2
and do not show deoxyribonucleic acid (DNA) degradation even in the presence of massive amounts of E
2
. However, when both endonuclease I and E
2
were present, spheroplast DNA was degraded by an endonucleolytic activity which gave rise primarily to double-strand DNA cleavages, producing fragments having an average molecular weight of 9 × 10
6
. Pancreatic ribonuclease could substitute for colicin E
2
in the reconstitution system, but pancreatic deoxyribonuclease could not replace endonuclease I. However, colicin E
2
could not activate transfer ribonucleic acid-inhibited endonuclease I in an in vitro system where pancreatic ribonuclease caused full stimulation.
Formation and Secretion of Induced Penicillinase in Protoplasts of
Staphylococcus aureus
Authors: Coles N. W. , Gross R.
Published: June 2012

Conditions suitable for induced formation and secretion of penicillinase (EC 3.5.2.6) in protoplasts of
Staphylococcus aureus
were determined. No requirement was found for cells to be exposed to inducer prior to formation of protoplasts. Neither cell wall components nor mesosomes appeared to be necessary for induction or secretion. In medium containing 1.1 M sucrose about half of the formed enzyme was soluble, whereas in medium containing 0.37 M sodium succinate only about 10% of the penicillinase remained protoplast-bound. Low concentrations of polyanions (dextran sulfate and potassium polyvinyl-sulfonate) inhibited the formation of induced penicillinase, as did 4-acetamido-4′-isothiocyano-stilbene 2,2′-disulfonic acid. None of these compounds inhibited the activity of native penicillinase, and none would be expected to pass through the protoplast membrane. Penicillinase, denatured in 4 M urea, could be renatured by dilution in the presence of benzylpenicillin, and the above three inhibitors interfered strongly with this process. The results are taken as evidence that penicillinase may be secreted through the protoplast membrane in an incompletely folded form.
In Vitro Studies of BB-K8, a New Aminoglycoside Antibiotic
Authors: Bodey Gerald P. , Stewart Dorothy
Published: June 2012

BB-K8, an aminoglycoside antibiotic which is a derivative of kanamycin, was tested in vitro against 466 clinical bacterial isolates. Over 90% of gram-negative bacilli, except
Proteus
spp., were inhibited by 3.12 μg of BB-K8 per ml. This antibiotic was consistently more active than kanamycin but less active than tobramycin or gentamicin. Unlike kanamycin, BB-K8 was active against
Pseudomonas aeruginosa
. Eleven of 19 isolates resistant to either gentamicin or tobramycin, or both, were susceptible to BB-K8.
Antibiotic Susceptibility of
Pseudomonas pseudomallei
Authors: Hall Wendell H. , Manion Robert E.
Published: June 2012

The in vitro activity of various antibiotics against
Pseudomonas pseudomallei
was studied. The tetracyclines were the most active, followed by gentamicin, kanamycin, novobiocin, chloramphenicol, rifampin, cycloserine, erythromycin, and ampicillin.
Studies on the Susceptibility of 150 Consecutive Clinical Isolates of
Pseudomonas aeruginosa
to Tobramycin, Gentamicin, Colistin, Carbenicillin, and Five Other Antimicrobials
Authors: Lockwood W. R. , Lawson Lucy A.
Published: June 2012

The in vitro susceptibilities of 150 clinical isolates of
Pseudomonas aeruginosa
to the aminoglycoside tobramycin and eight other antimicrobials were evaluated. The Food and Drug Administration standardized disk diffusion method showed that tobramycin inhibited 100% of the 150 isolates with gentamicin inhibiting only 90.7%. The difference between colistin (97.3%) and tobramycin was less marked. Carbenicillin (87.3%) was found to be slightly less active than gentamicin. Only a small percentage of the isolates were inhibited by the other drugs used. By using a minimal inhibitory concentration of 4 μg/ml in brain heart infusion broth as the level of susceptibility, it was found that only three of the isolates showed resistance to tobramycin, whereas 20 of the isolates were resistant to gentamicin. Approximately half of the isolates were inhibited by 0.5 μg/ml or less of tobramycin, whereas 1.5 μg of gentamicin per ml was required to inhibit 50% of susceptible strains.
Mode of Action of Lividomycin on Protein Synthesis in
Escherichia coli
Authors: Yamaguchi Masahito , Eda Junji , Kobayashi Fujio , Mitsuhashi Susumu
Published: June 2012

Lividomycin specifically inhibited bacterial protein synthesis and had codon misreading activity. Lividomycin, moreover, stimulated the binding of aminoacyl-transfer ribonucleic acid to ribosomes, but did not show any significant effects on the formation of aminoacyl-transfer ribonucleic acid and the puromycin reaction.
Variables Influencing Susceptibility Testing of
Cryptococcus neoformans
to 5-Fluorocytosine
Authors: Block Edward R. , Jennings Anne E. , Bennett John E.
Published: June 2012

The minimum inhibitory concentration (MIC) of 5-fluorocytosine (5-FC) was determined for 65 isolates of
Cryptococcus neoformans
by using a twofold serial tube dilution method. The MIC was profoundly influenced by incubation temperature, inoculum size, and duration of incubation. By using a standard set of test conditions, 100% of 49 pretreatment isolates of
C. neoformans
were susceptible to 10 μg of 5-FC per ml or less, and 9 (56%) of 16 isolates recovered during or after 5-FC therapy were massively drug resistant (MIC > 320 μg/ml). With the standard test conditions recommended here, the tube dilution method was found to be both accurate and reproducible, and the results correlated with the treatment status of patients.
Biosynthesis of Monensin
Authors: Day L. E. , Chamberlin J. W. , Gordee E. Z. , Chen S. , Gorman M. , Hamill R. L. , Ness T. , Weeks R. E. , Stroshane R.
Published: June 2012

The biosynthesis of monensin by
Streptomyces cinnamonensis
was studied by using
14
C-labeled glucose, acetate, propionate, butyrate, and methionine. The results indicated that the antibiotic is synthesized from five acetate, seven propionate, and one butyrate molecules. The
o
-methyl group of monensin is derived from methionine, whereas the terminal hydroxymethyl group is incorporated from acetate.
Compound 64716, a New Synthetic Antibacterial Agent
Authors: Wick W. E. , Preston D. A. , White W. A. , Gordee R. S.
Published: June 2012

Compound 64716, 1-ethyl-4 (1H)-oxo-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid, is a new synthetic antibacterial agent. The antibacterial spectrum of this compound includes gram-negative bacteria that are most frequently isolated from urinary tract infections. Minimal inhibitory concentration values of 64716 for isolates of
Escherichia coli
and
Proteus
sp. ranged from 2 to 4 and 2 to 8 μg/ml, respectively, and the compound was bactericidal at concentrations close to the minimal inhibitory concentration values. In vivo, doses required for successful therapy of experimental mouse infections were comparable to those for nalidixic acid. After oral administration of 40 mg/kg, peak concentrations of this compound in mouse blood reached 19.2 μg/ml. Within 30 min after doses of 20 mg/kg, bacteriologically active drug concentrations of 64716, nalidixic acid, and oxolinic acid in mouse urine were >1,000, 170, and <1.5 μg/ml, respectively. Resistant bacteria were not selected when bacteria were exposed to 500 μg/ml of 64716. Compound 64716 was less bound by human serum proteins than was nalidixic acid. Equivalent antibacterial activity along with superior pharmacological properties of 64716 when compared with nalidixic acid lead to the conclusion that this new compound is a promising antibacterial agent.
Antiviral Activity of Cytarabine in Herpesvirus–Infected Rats
Authors: Renis Harold E.
Published: June 2012

Intranasal inoculation of herpesvirus (approximately 1.8 mean lethal doses [LD
50
] in 0.1 ml) into 105- to 115-g rats produces paralytic disease in 4 to 5 days and 80 to 100% mortality in 8 to 12 days. Cytarabine (ara-C) (40 to 320 mg/kg), administered subcutaneously to inoculated rats, delays the onset of paralysis and protects the animals from death. Drug treatments were given twice daily for 5 days. Beneficial drug effects were observed even when initiation of therapy was delayed for 3 days after virus inoculation. A dose-response relationship existed when therapy was initiated at 4 h after virus inoculation. However, when therapy was delayed for 3 days, it appeared that the highest drug level (320 mg/kg twice daily) was somewhat less effective than the lower doses (160 and 80 mg/kg twice daily). Virus could be detected in homogenates of brain beginning 3 days after inoculation, and the titer increased through 7 days. Ara-C treatment, initiated 4 h after inoculation, caused a delay in the appearance of virus, and a reduction in the titer in the brain homogenates. No virus was detected in blood serum, or in homogenates prepared from lung, kidney, thymus, or spleen of infected rats. The virus titration studies are in agreement with the illness and mortality produced by herpesvirus infection.
Effects of Phosphonic Acid Analogues of Glycerol-3-Phosphate on the Growth of
Escherichia coli
: Phospholipid Metabolism
Authors: Shopsis Charles S. , Nunn William D. , Engel Robert , Tropp Burton E.
Published: June 2012

The effects of glycerol-3-phosphate, 3,4-dihydroxybutyl-1-phosphonate, and 2,3-dihydroxypropyl-1-phosphonate on the metabolism of
Escherichia coli
strains 8 and 1908 were determined. These strains lack the membrane-bound glycerol-3-phosphate dehydrogenase and are constitutive for the glycerol-3-phosphate transport system. Such cells were more sensitive to growth inhibition by the four-carbon phosphonate than by glycerol-3-phosphate. The three-carbon phosphonate did not appear to inhibit cell growth. The incorporation of labeled precursors of lipid, protein, ribonucleic acid, or deoxyribonucleic acid into bacterial cells was measured in the presence of either glycerol-3-phosphate or one of its phosphonic acid analogues. The phosphonic acid analogues inhibited the uptake of labeled acetate into the lipid fraction to the greatest extent. The incorporation of [
33
P]PO
4
into phospholipids was strongly inhibited by 3,4-dihydroxybutyl-1-phosphonate but was only slightly affected by 2,3-dihydroxypropyl-1-phosphonate. Glycerol-3-phosphate inhibited the incorporation of labeled uracil to the greatest extent during the first 20 min; however, this effect was largely reversed after 90 min. Only 3,4-dihydroxybutyl-1-phosphonate altered the distribution of labeled acetate into the phospholipids of strain 8, decreasing the percentage of counts in the phosphatidylglycerol fraction. The three-carbon phosphonate probably alters acetate incorporation by affecting the acetyl-coenzyme A pool, whereas the 3,4-dihydroxybutyl-1-phosphonate has a definite effect upon phospholipid metabolism. It is suggested that
l
-glycerol-3-phosphate:cytidine monophosphate phosphatidyltransferase is the probable site of action.
Pharmacokinetics of Cephanone in Healthy Adult Volunteers
Authors: Regamey Claude , Kirby William M. M.
Published: June 2012

Five volunteers received intramuscular injections of 7 mg (approximately 500 mg) of cephanone, a new cephalosporin for parenteral use per kg. Peak serum concentrations averaged 36 μg/ml, about four times as high as with the same doses of cephalothin, twice as high as with cephaloridine, and slightly lower than with cefazolin. With a constant intravenous infusion of 100 mg/h, a steady-state serum concentration of 31 μg/ml was attained in four volunteers. The serum half-life was similar for the intramuscular and intravenous studies, 2.4 and 2.6 h, respectively. Over 90% of the dose administered was recovered in the urine. The factor mainly responsible for the higher and more sustained serum concentrations of cephanone was its low renal clearance of 47 ml per min per 1.73 m
2
. Cephanone has a small apparent volume of distribution, probably related to its high serum protein binding of 88%.
Effects of Rifamycin Derivatives, Alone and in Combination with Amphotericin B, Against
Histoplasma capsulatum
Authors: Kobayashi George S. , Cheung Sze-Schuen C. , Schlessinger David , Medoff Gerald
Published: June 2012

Several derivatives of rifamycin SV inhibited ribonucleic acid synthesis and decreased the viability of
Histoplasma capsulatum
. Both of these effects were enhanced by low concentrations of amphotericin B. The relative potency of the different rifamycin derivatives against
H. capsulatum
, when used in combination with amphotericin B or alone, was the same as that reported for the inhibition of the reverse transcriptase of ribonucleic acid tumor viruses.
Cephradine: Absorption, Excretion, and Tissue Distribution in Animals of a New Cephalosporin Antibiotic
Authors: Weliky I. , Gadebusch H. H. , Kripalani K. , Arnow P. , Schreiber E. C.
Published: June 2012

Metabolic studies were conducted with cephradine administred by the oral, subcutaneous, intravenous, or rectal routes to mice, rats, and dogs. Peak blood levels were usually attained in 30 to 150 min after dosing, depending on the animal species studied. Based on urinary excretion, cephradine appeared to be well absorbed after oral or subcutaneous administration; after rectal doses, cephradine was absorbed poorly. In rats and dogs given oral or intravenous doses of cephradine, about 70 to 100% of the administered dose was recovered during a 24-h collection period. Cephradine was excreted unchanged. After the oral or intravenous administration of [
3
H]cephradine to rats and dogs, respectively, its plasma half-life was about 1 h. After oral administration to rats, cephradine was distributed widely throughout the body tissues, with the greatest concentrations in the kidneys and liver; at 45 min to 6 h postdose, cephradine concentrations in the kidneys and liver were about 8 and 3 times higher, respectively, than those in plasma.
Biological Assay of Streptonigrin (NSC 45383) in Body Fluids and Tissues of Mice
Authors: Pittillo Robert F. , Woolley Carolyn
Published: June 2012

Streptonigrin, a quinone antitumor antibiotic, has been reported to be effective in human trials. A sensitive and precise microbiological assay for the determination of distribution and concentrations of streptonigrin in the body fluids and tissues of treated mice has been developed in an attempt to supplement successful clinical application of this drug.
Comparative Therapeutic and Pharmacological Evaluation of Amoxicillin and Ampicillin Plus Probenecid for the Treatment of Gonorrhea
Authors: Karney Walter W. , Turck Marvin , Holmes King K.
Published: June 2012

Single doses of 3.5 g of ampicillin with 1.0 g of probenecid or of 3.0 g of amoxicillin alone were administered orally to 58 males and 56 females with uncomplicated gonococcal infection. The failure rate for genital or anal infection, or both, was 1.7% for ampicillin plus probenecid and 4.2% for amoxicillin alone. However, patients with oropharyngeal infection responded poorly. Seventy-five isolates of
Neisseria gonorrhoeae
recovered from patients in this study were all inhibited by 1.0 μg or less of ampicillin or amoxicillin per ml; penicillin G, ampicillin, and amoxicillin had similar activity in vitro against these isolates. Serum concentrations of amoxicillin in 10 volunteers remained above the minimal inhibitory concentration for most strains of
N. gonorrhoeae
for periods up to 10 h after a 3.0-g oral dose. After 2.0 g of ampicillin was given with probenecid, the serum levels during the 5- to 12-h period approached those achieved with 3.5 g of ampicillin plus probenecid, and actually exceeded levels attained during the same interval with 3.0 g of amoxicillin administered alone.
Comparative Clinical Study of Tobramycin and Gentamicin
Authors: Klastersky J. , Hensgens C. , Henri A. , Daneau D.
Published: June 2012

Gentamicin and tobramycin have been compared in vitro and as single-drug therapy in patients with a serious infection caused by gram-negative rods. In vitro, a slight advantage of tobramycin over gentamicin has been found against
Pseudomonas aeruginosa
. Cross-resistance between gentamicin and tobramycin has been observed for gentamicin-resistant strains of
P. aeruginosa
and
Providence
but was not always present. The clinical effectiveness of gentamicin and tobramycin was similar: 14 (45.1%) out of the 31 patients in each series responded favorably. The clinical results were much better in urinary tract infections (66% of favorable responses) than in wound infections, pulmonary infections, septicemia, and meningitis (26% of favorable responses). The frequency of adverse reactions encountered in the present series was similar for both drugs.
Double-Blind Comparison of Cephacetrile with Cephalothin/Cephaloridine
Authors: Jackson George Gee , Riff Louise J. , Zimelis Victoria M. , Daood Mohammad , Youssuf Mohammad
Published: June 2012

Under double-blind protocol, a controlled comparison was made between a new cephalosporin, cephacetrile, and cephalothin or cephaloridine. The patient's primary physician determined the indications for treatment, and the dosage was uniform for each route of administration. Infecting strains of staphylococci and
Proteus mirabilis
had a lower median inhibitory concentration for cephalothin than cephacetrile; the opposite was true for
Escherichia coli
and
Klebsiella
species. The average peak serum level 1 h after a dose of 2 g intravenously was 74.9 ± 21 and 21.5 ± 8.7 μg/ml for cephacetrile and cephalothin, respectively; 6 h after the dose, the respective levels were 12.4 ± 4.3 and 3.7 ± 0.9 μg/ml. Renal clearances were similar and the plasma clearance was proportional to the serum levels. In the urine, the concentration of cephacetrile was three times higher than that of cephalothin. Based on a percentage of therapeutic potential, success in the treatment of infections with susceptible organisms was 42 and 44% for the two different drug regimens. Initial bacterial resistance was found in about one-fifth of infections, and concomitant therapy with other drugs was practiced in one-half of the treatment courses. Intravenous use of cephacetrile was discontinued prematurely more often than was use of cephalothin, suggesting less tolerance. Although there was no overt toxicity, more than 75% of patients on either regimen had some form of unwanted response to treatment, the most common being superinfection. From this limited but controlled experience, cephacetrile can be considered comparable to cephalothin in antimicrobial treatment and overall side reactions.
Antibiotics as Probes of Ribosome Structure: Binding of Chloramphenicol and Erythromycin to Polyribosomes; Effect of Other Antibiotics
Authors: Pestka Sidney
Published: June 2012

Antibiotics were used as probes of ribosome topology and function. Studies of [
14
C]chloramphenicol and [
14
C]erythromycin binding to ribosomes and polyribosomes revealed the following features. The requirement of high K
+
concentration (150 mM) for [
14
C]chloramphenicol binding to NH
4
Cl-washed ribosomes resulted from the washing procedure. Neither native 70
S
ribosomes nor polyribosomes require K
+
greater than 30 mM for [
14
C]chloramphenicol binding. Whereas [
14
C]chloramphenicol binds to both ribosomes and polyribosomes, [
14
C]erythromycin binds essentially only to ribosomes. After removal of peptidyl-transfer ribonucleic acid (tRNA) from polyribosomes, [
14
C]erythromycin could then be bound. The effects of a number of antibiotics on [
14
C]chloramphenicol binding to ribosomes and polyribosomes was assessed. It was found that most of the macrolides (erythromycin, carbomycin, spiramycin III, niddamycin, oleandomycin, and tylosin) and streptogramins A and B (vernamycin A, PA114A, vernamycin Bα, and PA114B) inhibited chloramphenicol binding to NH
4
Cl-washed and native 70
S
ribosomes, but not to polyribosomes. After removal of peptidyl-tRNA from polyribosomes, [
14
C]chloramphenicol binding was then inhibited. In contrast, sparsomycin and althiomycin inhibited chloram-phenicol binding to polyribosomes, but not to ribosomes. After removal of peptidyl-tRNA from polyribosomes, sparsomycin and althiomycin were then ineffective. The presence of peptidyl-tRNA on polyribosomes apparently is required for binding of sparsomycin and althiomycin, but prevents binding of most macrolides and streptogramins. The lincosaminides (lincomycin and celesticetin) and methymycin (a small macrolide) inhibited [
14
C]chloramphenicol binding to NH
4
Cl-washed and native 70
S
ribosomes best, but also inhibited the binding to polyribosomes. The amino nucleosides and other antibiotics tested do not seem to interact strongly with the major chloramphenicol-binding site. These results provide knowledge of the interrelationships between antibiotic and substrate ribosome binding sites which should eventually contribute to a map of ribosomal topology.
Rosamicin: Evaluation In Vitro and Comparison with Erythromycin and Lincomycin
Authors: Crowe Christine C. , Sanders W. Eugene
Published: June 2012

Rosamicin is a new macrolide antibiotic produced by
Micromonospora rosaria
. It shares certain chemical and biological characteristics with erythromycin. Activity against gram-positive strains was assayed by broth dilution and compared to that of erythromycin and lincomycin. Rosamicin was bacteriostatic and inhibited most strains of
Staphylococcus aureus, Staphylococcus epidermidis
, enterococci, viridans streptococci, and group A streptococci in concentrations of 0.02 to 4.0 μg/ml. Results were similar for erythromycin and for lincomycin (excluding enterococci). Cross-resistance of gram-positive organisms to these three antimicrobial agents was incomplete. Rosamicin was more active than erythromycin against
Enterobacteriaceae
and
Pseudomonas
at pH 7.2. Alkalinization of the medium enhanced the activity of both rosamicin and erythromycin; however, rosamicin was still more active than erythromycin against all gram-negative strains at pH 7.6 and 8.0. In view of the high degree of in vitro activity of rosamicin against gram-positive organisms, lack of complete cross-resistance with erythromycin and lincomycin, and the greater activity of rosamicin than erythromycin against gram-negative organisms, further investigation of this macrolide is warranted.
Treatment of Anaerobic Bacterial Infections with Clindamycin-2-Phosphate
Authors: Levison Matthew E. , Bran Jose L. , Ries Kristen
Published: June 2012

Thirty-five patients with a variety of serious infections caused by anaerobic bacteria responded to clindamycin. Cure was achieved in 27 of the 32 patients with pleuropulmonary and intra-abdominal infections. Mean serum concentrations of clindamycin for the 8 h after intramuscular administration of clindamycin in these patients were at least 2.5 times the minimal inhibitory concentration of clindamycin for more than 90% of anaerobes. This experience suggests that clindamycin is an excellent and relatively safe antibiotic for treatment of infection caused by anaerobes when combined with surgery (when indicated) or other antibiotics active against aerobic gram-negative bacilli, if present.
Effect of Pipecolic Acid Isomers on the Biogenesis of Actinomycins
Authors: May W. Stratford , Formica Joseph V.
Published: June 2012

Streptomyces antibioticus
produces a family of actinomycin components which differ solely at the “imino acid” site of the molecule; however, new congeners of actinomycin are synthesized when cultures are supplemented with pipecolic acid (PA). The quantitative and qualitative nature of the actinomycins produced differed when cultures were incubated in the presence of either
l
-,
d
-, or racemic PA. In the presence of
d
-PA, the quantitative and qualitative nature of those actinomycins produced were similar to those produced in the absence of supplementation. By contrast, in the presence of
l
-PA or
dl
-PA new actinomycin components containing PA were synthesized at the expense of normally produced components. Also, the total amount of antibiotic produced decreased in response to increasing concentrations of exogenously supplied
l
-PA. This effect occurred whether or not
d
-PA was also added to cultures. Concentrations of
l
-PA greater than 125 μg/ml of medium resulted in no additional decrease in the amount of antibiotic produced. Although PA-containing actinomycins were formed as early as 6 h after the addition of 250 μg of
l
-PA per ml, it was not until 24 h postaddition that the relative percentages of actinomycin components produced approached a constant value. Evidence presented here indicated that the
l
-isomer of PA replaces
l
-proline in the pentapeptide of actinomycin.
R Factors in Strains of
Salmonella typhi
and
Shigella dysenteriae
1 Isolated During Epidemics in Mexico: Classification by Compatibility
Authors: Datta Naomi , Olarte J.
Published: June 2012

All 17
Salmonella typhi
strains tested from the epidemic in Mexico carried R factors of compatibility group H, conferring resistance to chloramphenicol, streptomycin, tetracycline, and sulfonamides. Some
S. typhi
strains carried, in addition, non-conjugative, ampicillin resistance plasmids and R factors of the I or A–C complex. All 20
Shigella dysenteriae
1 strains tested of epidemic origin carried O-group R factors. Ampicillin resistance in
S. dysenteriae
1 was not proved to be plasmid borne. R factors of group H were not identified in any of the tested Mexican isolates other than
S. typhi
, but R factors of group O were identified in
Escherichia coli, Shigella flexneri
, and one strain of
S. typhi
, as well as in the epidemic
S. dysenteriae
. An R factor was identified which seemed to have two compatibility specificities, groups Iω and O.
Entry of Four Tetracyclines into Saliva and Tears
Authors: Hoeprich Paul D. , Warshauer David M.
Published: June 2012

Although meningococci are susceptible to the tetracyclines by testing in vitro, oxytetracycline (OC) and doxycycline (DC) have failed to eliminate carriage, whereas minocycline (MC) has been effective. Because these congeners differ in lipophilicity, they and tetracycline (TC) were studied in volunteers by assay of serum, saliva, and tears obtained after 5 days of treatment. OC and TC were undetectable or attained concentrations subinhibitory for meningococci in saliva and tears. The concentrations of MC in saliva and tears were equal to or greater than the average minimal inhibitory concentration as long as 12 h post-dose. Near inhibitory concentrations resulted with DC at 100 mg/day; yet, doubling the dose to 100 mg/12 h did not yield concentrations that exceeded the average minimal inhibitory concentration for meningococci. The previous reports of failure or meager entry of DC and MC into saliva probably reflected extraction of these drugs in the paraffin chewed by subjects to stimulate salivary flow. The efficiency of entry of the tetracyclines into the secretions of the noninflamed upper respiratory tract correlates with lipophilicity at physiological pH, enabling prediction of meningococcal chemoprophylactic efficacy.
Alterations in Dihydropteroate Synthetase in Cell-Free Extracts of Sulfanilamide-Resistant
Neisseria meningitidis
and
Neisseria gonorrhoeae
Authors: Ho Richard I. , Corman Leonard , Morse Stephen A. , Artenstein Malcolm S.
Published: June 2012

Extracts from
Neisseria meningitidis
and
N. gonorrhoeae
with varying susceptibility to sulfanilamide have been investigated for dihydropteroate synthetase activity. Sulfanilamide was a competitive inhibitor of dihydropteroate synthetase with respect to
p
-aminobenzoate in extracts from both species. Though the

K
m

for
p
-aminobenzoate was unaffected, the

K
i

for sulfanilamide increased and the

V
max

decreased as the strains' resistance to sulfanilamide increased. Temperature studies have revealed differences in the dihydropteroate synthetase from
N. meningitidis
and
N. gonorrhoeae
. A direct relationship was observed between the minimal inhibitory concentration of sulfanilamide determined in vitro and the ratio of

K
i
/K
m

. This ratio may be a molecular explanation of sulfanilamide resistance for both
N. meningitidis
and
N. gonorrhoeae
.
Effect of Certain Polypeptides on the Biological Activities of Measles Virus
Authors: Norrby Erling , Sievertsson Hans
Published: June 2012

The effect of a selected tripeptide, Z-
d
-Phe-Phe-Arg(NO
2
) (SV-4814) on the kinetics of lysis of green monkey erythrocytes by measles virus hemolysin suggested conditions of competitive inhibition. SV-4814 prevented not only hemoglobin release, but also the preceding leakage of K
+
through the cell membrane. The capacity of 12 different dipeptides, 6 tripeptides, including SV-4814, and 4 tetrapeptides to inhibit measles virus-specific hemolysis and infectivity was analyzed. Tri- and tetrapeptides were more active than dipeptides. The presence of aromatic amino acids and a free carboxyl terminal appeared to be a prerequisite for inhibitory activity. Two compounds, one tripeptide (Z-Phe-
d
-Phe-
d
-Tyr) and one tetrapeptide [Z-
d
-Phe-Arg(NO
2
)-
d
-Met], carried an inhibitory activity, which was about two times higher than that of SV-4814.
In Vitro Susceptibility of
Shigella
Strains to Trimethoprim and Sulfamethoxazole
Authors: Rudoy Raul C. , Nelson John D. , Haltalin Kenneth C.
Published: June 2012

Trimethoprim and sulfamethoxazole were tested alone and in combination against 227 recently isolated
Shigella
strains. Variations in medium constituents and inoculum size were used to determine the optimal testing conditions. The plate dilution method with addition of 5% lysed horse blood to the susceptibility test medium and an inoculum size of 10
2
organisms was found to provide satisfactory results. All 227 strains were inhibited by low concentrations of trimethoprim, and all were susceptible to the combination of 0.06 μg of trimethoprim per ml and 1.25 μg of sulfamethoxazole per ml. Sixteen percent of these strains were resistant to ampicillin, 33% to tetracycline, 15% to chloramphenicol, and 27% to cephalothin. Based on these in vitro observations, trimethoprim and sulfamethoxazole appear worth evaluating for treatment of shigellosis due to multiply antibiotic-resistant strains.
Mutations in
Escherichia coli
K-12 Decreasing the Rate of Streptomycin Uptake: Synergism with R-Factor-Mediated Capacity to Inactivate Streptomycin
Authors: Lundbäck Annika K. , Nordström Kurt
Published: June 2012

Escherichia coli
K-12 carrying the R-factor R1 or R6K is resistant to streptomycin. The resistance is due to R-factor-coded enzymes that metabolize the drug. Streptomycin can be inactivated in two ways, either by adenylylation or by phosphorylation; both reactions require adenosine 5′-triphosphate. In this work we show that the R-factor R1 codes for an enzyme that adenylylates streptomycin and that the enzyme activity is located in the periplasmic volume, whereas the R-factor R6K codes for a streptomycin phosphorylase, which is mainly cytoplasmic. From a strain without any R-factor or carrying different R-factors, mutants were isolated that are 10 times more resistant to streptomycin than the parent strains. This increased resistance is not due to increased amounts of metabolizing enzymes. The mutants have a decreased rate of uptake of streptomycin and an altered response to other antibacterial agents as well. The mutations are located on the chromosome and not on the plasmid. It is likely that the mutations cause changes in the outer layers of the cell envelope and that the increased resistance is due to the synergistic effect of an efficient penetration barrier and a low activity of inactivating enzyme.
Enzymatic Inactivation of a New Aminoglycoside Antibiotic, Sisomicin, by Resistant Strains of
Pseudomonas aeruginosa
Authors: O'Hara K. , Kono M. , Mitsuhashi S.
Published: June 2012

The antibacterial activity of sisomicin (SS), a new aminoglycoside antibiotic active toward clinical isolates of
Pseudomonas aeruginosa
, was determined and compared with that of the gentamicin C complex. Both drugs were effective against these strains and showed almost the same antibacterial activity. A few strains were found to be resistant to SS. The antibiotic was inactivated by a cell-free extract from the SS-resistant strains due to acetylation of the drug. Comparative studies of the inactivation of the drugs which lack a 6′-amino group in the amino sugar linked to 2-deoxystreptamine strongly suggested that SS inactivation was due to acetylation of the 6′-amino group of the 4′,5′-didehydropurpurosamine moiety.
Gentamicin-Adenylyltransferase Activity as a Cause of Gentamicin Resistance in Clinical Isolates of
Pseudomonas aeruginosa
Authors: Kabins S. , Nathan C. , Cohen S.
Published: June 2012

Gentamicin adenylyltransferase activity was found in extracts of clinical isolates of gentamicin-resistant
Pseudomonas aeruginosa
. Extracts of one of these isolates,
P. aeruginosa
POW, inactivated gentamicin in the presence of adenosine 5′-triphosphate. Extracts of strain POW catalyzed the binding of radioactivity from [
14
C]adenine adenosine 5′-triphosphate to gentamicin components, tobramycin, sisomicin, kanamycin A and B and, to a variable degree, streptomycin and spectinomycin. The substrate profile with these agents and other aminocyclitols was similar to that obtained with R factor-mediated gentamicin adenylyltransferase found in
Enterobacteriaceae
. Adenylylating activity was absent in gentamicin-susceptible mutants of strain POW. Adenylylation may be added to acetylation as an enzymatic mechanism responsible for gentamicin resistance among strains of
P. aeruginosa
.
In Vitro Comparison of Four Aminoglycoside Antibiotics: Sisomicin, Gentamicin, Tobramycin, and BB-K8
Authors: Levison Matthew E. , Kaye Donald
Published: June 2012

The activity of sisomicin, gentamicin, and tobramycin against 273 clinical bacterial isolates was about equal (except for greater activity of tobramycin against
Pseudomonas
) and was greater than that of BB-K 8 as determined by antibiotic dilution methods in agar and broth.
In Vitro Antimalarial Activity of Nucleic Acid Precursor Analogues in the Simian Malaria
Plasmodium knowlesi
Authors: McCormick Gerald J. , Canfield Craig J. , Willet Gloria P.
Published: June 2012

Analogues of nucleic acid precursors were screened for antimalarial activity in
Plasmodium knowlesi
by using an in vitro culture system. Activity was assessed by the degree of inhibition of incorporation of
l
-[
methyl
-
14
C]methionine into protein and of [8-
14
C]adenosine and [6-
14
C]orotic acid into ribonucleic acid and deoxyribonucleic acid. The incorporation of adenosine or orotic acid was effectively inhibited by many of the compounds, including 3′ analogues of purine nucleosides, many of the 6-position analogues of purine bases and nucleosides, and 5-position analogues of orotic acid. Only a few compounds inhibited methionine incorporation into protein, and in each instance adenosine or orotic acid incorporation also was inhibited. Some compounds inhibited adenosine or orotic acid incorporation into both ribonucleic acid and deoxyribonucleic, whereas other analogues inhibited incorporation into one nucleic acid only. The qualitative and quantitative differences suggest that this experimental system may be appropriate for investigation of metabolic pathways of the malaria parasite, as well as for demonstration of antimalarial activity of candidate antimalaria drugs.