bluuebunny/crossref_metadata_2025 huggingface dataset:
Cefoxitin, a Semisynthetic Cephamycin Antibiotic: In Vivo Evaluation
Authors: Miller A. Kathrine , Celozzi Evemarie , Kong Yulin , Pelak Barbara A. , Hendlin David , Stapley Edward O.
Published: June 2012

Cefoxitin, 3-carbamoyloxymethyl-7-α-methoxy-7-[2-(2-thienyl)acetamido]-3-cephem-4- carboxylic acid, a semisynthetic cephamycin antibiotic shown to have broad-spectrum activity in vitro, is active also in vivo against a wide variety of bacteria including penicillin-resistant staphylococci. It is, however, particularly effective against gram-negative organisms including strains of indole-positive
Proteus
against which cephalothin and cephaloridine are ineffective. When cefoxitin is given subcutaneously, concentrations in mouse blood, urine, and other tissues are higher than those seen for cephalothin. Higher concentrations in the blood and greater therapeutic efficacy are achieved with cefoxitin when it is given with probenecid. For this reason it is believed that cefoxitin is excreted mainly by way of the renal tubules. The data indicate that cefoxitin has potential as a therapeutically useful antibiotic.
Susceptibility of Related Vibrios and
Vibrio Fetus
to Twelve Antibiotics
Authors: Butzler J. P. , Dekeyser P. , Lafontaine T.
Published: June 2012

One hundred fourteen strains of related vibrio and seven strains of
Vibrio fetus
, all isolated from humans, were tested for susceptibility in vitro to 12 antibiotics. Mueller-Hinton agar containing 14 dilutions of the antibiotics was inoculated with undiluted overnight cultures. Gentamicin and erythromycin were the most active drugs against related vibrios and
Vibrio fetus
; lower activity was noted with chloramphenicol, streptomycin, and tetracycline; neomycin and kanamycin were even less active. The susceptibility to ampicillin was variable. More than 90% of the strains were resistant to cephalothin.
Susceptibility of 1,500 Isolates of
Pseudomonas aeruginosa
to Gentamicin, Carbenicillin, Colistin, and Polymyxin B
Authors: Duncan Ian B. R.
Published: June 2012

A series of 1,500 strains of
Pseudomonas aeruginosa
was collected from a variety of sources to provide a group of strains which would truly represent the species. All of them were pyocine typed, and a wide range of types was included among the isolates from each source. The gentamicin, carbenicillin, colistin, and polymyxin minimal inhibitory concentration of each strain was measured by the agar dilution method employing the Steers inocula replicator. Over 99% of strains were inhibited by 8 μg of gentamicin per ml, by 256 μg of carbenicillin per ml, and by 4 μg of colistin per ml. The small number of strains more resistant to each antibiotic comprised a variety of different pyocine types. Few strains were found to be susceptible to tetracycline, chloramphenicol, kanamycin, or streptomycin at the single concentration tested.
Quantitative Assay of Pyrazofurin a New Antiviral, Antitumor Antibiotic
Authors: Westhead J. E. , Price H. D.
Published: June 2012

Pyrazofurin, a carbon-linked nucleoside, has been previously reported to possess antiviral and antitumor activity. The antagonistic effect of pyrazofurin against
Neurospora crassa
has been utilized to develop a quantitative assay for the compound.
Biosynthesis of Fosfomycin by
Streptomyces fradiae
Authors: Rogers Thomas O. , Birnbaum Jerome
Published: June 2012

The antibiotic fosfomycin was produced as a secondary metabolite in a glucose-asparagine medium containing citrate,
l
-methionine, and
l
-glutamate. The citrate requirement for antibiotic synthesis was related to its requirement for growth. In contrast,
l
-methionine and
l
-glutamate caused a marked stimulation of fosfomycin production and had no effect on growth.
l
-Methionine had to be added early to effect maximal antibiotic synthesis later in the fermentation. The
l
-glutamate requirement was not specific, since several tricarboxylic acid cycle intermediates could replace this amino acid.
l
-Asparagine was the most effective nitrogen source for growth and production of fosfomycin. Glycine, an alternate nitrogen source, supported fosfomycin synthesis only when added in excess of that needed for growth. Cobalt and inorganic phosphate were required also for antibiotic production at concentrations exceeding those supporting maximal growth. Radioactive incorporation studies showed that the methyl carbon of methionine was the precursor of the methyl of fosfomycin. Carbon 1 of fosfomycin was derived from glucose carbons 1 and 6, whereas glucose-
2
-
14
C
labeled fosfomycin carbon 2. Radioactivity from acetate-
2
-
14
C
was distributed equally between fosfomycin carbons 1 and 2. No incorporation of acetate-
1
-
14
C
, asparagine-
U
-
14
C
, citrate-
1,5
-
14
C
, or glutamate-
U
-
14
C
occurred. The labeling pattern of fosfomycin carbons 1 and 2 was similar to that found in 2-aminoethylphosphonate from
Tetrahymena
.
Activity of BB-K8 (Amikacin) Against Clinical Isolates Resistant to One or More Aminoglycoside Antibiotics
Authors: Price K. E. , Pursiano T. A. , DeFuria M. D. , Wright G. E.
Published: June 2012

One hundred fifty-two bacterial strains that possess resistance to kanamycin A, gentamicin, or tobramycin, or to more than one of these antibiotics, were collected from various sources in Canada, Europe, Japan, and the United States. This collection was composed of
Staphylococcus aureus
and
Pseudomonas aeruginosa
and members of the
Enterobacteriaceae
family. Their susceptibility to BB-K8 (amikacin), a new broad-spectrum semisynthetic derivative of kanamycin A, and to the other agents, was determined on Mueller-Hinton Medium by the twofold agar dilution method. Test results revealed that 60.5% of the isolates were resistant to 8 μg of tobramycin per ml, 67.1% to 8 μg of gentamicin per ml, 86.2% to 20 μg of kanamycin A per ml, and only 8.6% to 20 μg of amikacin per ml. Of interest is the fact that the amikacin-resistant strains were generally resistant to all of the other aminoglycosides. The broad spectrum of amikacin was not totally unexpected, because the compound has been shown to be a poor substrate for most enzymes that inactivate other aminoglycosides through
O
-phosphorylation,
O
-adenylylation, or
N
-acetylation. A number of susceptibility profiles were obtained when the organisms were tested against a series of nine aminoglycosides. The majority of these profiles resembled those found for organisms that possess known mechanisms of enzymatic inactivation.
Anti-Herpesvirus Action of Isoprinosine
Authors: Gordon Paul , Ronsen Bruce , Brown Eric R.
Published: June 2012

Anti-herpesvirus effects of Isoprinosine were found to be condition-dependent in vitro and in vivo. A herpes type 1 strain, grown in primary rabbit kidney cells, was not susceptible to Isoprinosine when cytopathic effect was evaluated, but was modestly inhibited when plaque-forming methocel overlay was used in the same cell line. However, the growth of a herpes type 2 strain was inhibited by Isoprinosine in this system when cytopathic effect was evaluated. Both viruses produced an encephalitis in hamsters after application by corneal abrasion. The encephalitis produced by a 1.5 mean lethal dose of herpesvirus was strikingly suppressed by large doses of Isoprinosine given ad libitum in the drinking water; this protection was not seen, however, at 15 mean lethal doses. Anti-herpes effects of Isoprinosine were suppressed by additional treatment with cortisone, both in tissue culture and in vivo. Isoprinosine, in the absence of virus infection, produced significant effects on the metabolism, structure, and function of brain ribosomes. In vivo, RNA components were labeled more rapidly and gave up their radioactivity more slowly after treatment with Isoprinosine. This enhanced cytoplasmic radioactivity was associated with a loss of incorporated radioactivity located in the nucleus and an increase in radioactivity located in a ribonucleo-protein fraction >4
S
and <18
S
. Ribosomes from treated brains gave physical evidence of being more compact (less orthochromic). Isoprinosine treatment increased the incorporation of [
14
C]phenylalanine into nascent protein in a cell-free system examining protein synthesis in brain polyribosomes. The addition of the exogenous messenger ribonucleic acid, polyuridylic acid, produced a significant age-dependent inhibition in the incorporation of [
14
C] phenylalanine. This inhibition was significantly greater when ribosomes were isolated from animals pretreated with Isoprinosine. These and other observations suggest that the Isoprinosine stimulation of host ribonucleic acid metabolism may be coupled to the production of ribosomes that do not effectively translate exogenous messenger ribonucleic acid.
Antibiotic Disk Susceptibility Tests with
Neisseria gonorrhoeae
Authors: Maier Thomas W. , Beilstein Henry R. , Zubrzycki Leonard
Published: June 2012

We have used a standardized disk diffusion procedure to test the susceptibility of 892 isolates of
Neisseria gonorrhoeae
to six antibiotics. The disk diffusion test described is a modification of the disk test of Bauer, Kirby, Sherris, and Turck, which is widely used for susceptibility testing of fast-growing, aerobic pathogens. With all six antibiotics (penicillin, ampicillin, tetracycline, erythromycin, chloramphenicol, and cephaloridine), disk test results were found to be reproducible and correlated well with the minimal inhibitory concentration as determined by an agar dilution procedure. The coefficients of correlation ranged from −0.79 with cephaloridine to −0.93 with penicillin. The technique described for disk susceptibility testing of gonococci can be used both for research and clinical purposes.
Dissociation Between Results of In Vitro and In Vivo Antibiotic Susceptibility Tests for Some Strains of
Pseudomonas aeruginosa
Authors: Davis Starkey D.
Published: June 2012

The relative efficacy in vivo of the polymyxin and aminoglycoside antibiotics in experimental
Pseudomonas
infection has apparently never been established. This study was designed to determine such efficacy in experimental infection of mice. Eleven strains of
Pseudomonas aeruginosa
were selected for the study, representing six of the seven recognized immunotypes. All strains were susceptible to colistin, gentamicin, and tobramycin in vitro, and all were virulent for mice. None was lethal because of preformed toxins. Infections were established in mice by intraperitoneal (i.p.) injection of 100 ID
50
of bacteria (infectious doses that would kill 50% of the mice). Graduated doses of antibiotics or saline were given subcutaneously 1 h later. Infections by three strains of
P. aeruginosa
were cured by low doses of all three antibiotics. Infections by two strains were relatively resistant in vivo to all three antibiotics. Infections by seven strains were relatively resistant in vivo to colistimethate. For most strains, colistimethate was less effective in vivo than gentamicin or tobramycin. To determine the influence of the size of the bacterial inoculum upon the results of chemotherapy, groups of mice were infected with serial dilutions of bacterial suspensions and treated with antibiotics. The antibiotics were more effective when a lighter bacterial inoculum was used. However, colistimethate at 30 mg/kg failed to cure some infections established with an inoculum of only 10 ID
50
. To examine the possibility that death despite apparently adequate chemotherapy might be due to bacterial lysis and delayed release of toxins, numbers of viable bacteria in the peritoneal cavity of treated animals were determined by colony count. Antibiotic failure by colistimethate was associated with a steady rise in the number of i.p. bacteria. The findings support the conclusion that i.p. infections in mice with some strains of
P. aeruginosa
that are fully susceptible in vitro are relatively resistant to chemotherapy in vivo. The dissociation between in vitro and in vivo results was greatest for colistimethate.
Human Pharmacology of 6-[
d
-α-(3-Guanylureido)-Phenylacetamido]- Penicillanic Acid (BL-P1654)
Authors: Bodey Gerald P. , Horikoshi Noboru , Rodriguez Victorio
Published: June 2012

BL-P1654 is a new α-substituted ureido penicillin which has broad-spectrum activity. Doses of 0.5 and 1.0 g administered by rapid intravenous injection produce mean peak serum concentrations of 40.7 and 80.8 μg/ml, respectively. The same doses administered by 1-h intravenous infusions produce mean peak serum concentrations of 22.6 and 47 μg/ml, respectively. The mean serum concentrations from 1 to 6 h after onset of administration of the drug are the same for both schedules. The mean serum concentration at 6 h after the rapid intravenous injection of 0.5- and 1.0-g doses of BL-P1654 are 3.4 and 5.4 μg/ml, respectively. A dose of 1.0 g every 4 h maintains a serum concentration of about 15 μg/ml. About 50 to 65% of the BL-P1654 is excreted in the urine during the first 6 h.
Molecular Basis for the Selective Toxicity of Amphotericin B for Yeast and Filipin for Animal Cells
Authors: Kotler-Brajtburg Janina , Price H. D. , Medoff Gerald , Schlessinger David , Kobayashi George S.
Published: June 2012

Among the polyene antibiotics, many, like filipin, cannot be used clinically because they are toxic; amphotericin B, however, is useful in therapy of human fungal infections because it is less toxic. Both the toxicity of filipin and the therapeutic value of amphotericin B can be rationalized at the cellular and molecular level by the following observations: (i) these polyene antibiotics showed differential effects on cells; filipin was more potent in lysing human red blood cells, whereas amphotericin B was more potent in inhibiting yeast cell growth; and (ii) the effects of filipin were more efficiently inhibited by added cholesterol, the major membrane sterol in human cells, whereas the effects of amphotericin B were more efficiently inhibited by ergosterol, the major membrane sterol in yeast. The simplest inference is that the toxicity and effectiveness of polyenes are determined by their relative avidities for the predominant sterol in cell membranes.
Effect of Ethylenediaminetetraacetic Acid and Related Chelating Agents on Whole Cells of Gram-Negative Bacteria
Authors: Haque H. , Russell A. D.
Published: June 2012

The effects of ethylenediaminetetraacetic acid and of four other chelating agents on seven strains of gram-negative bacteria are described. Changes in viability, cell lysis, and release of intracellular materials from suspensions in various buffers, pH 7.8 or 9.2, were observed. Cyclohexane-1,2-diaminotetraacetic acid was the most toxic compound, whereas iminodiacetic acid and nitrilotriacetic acid had little bactericidal activity. The activity of the five drugs appeared to be related to their chelating ability. Of the bacterial strains used,
Pseudomonas aeruginosa
NCTC 1999 and NCTC 6750 were the most susceptible, and
Klebsiella aerogenes
K1 was the most resistant. In contrast, the two strains of
P. aeruginosa
were the most resistant to the nonchelating antibacterial agents cetrimide, chlorhexidine, and benzalkonium chloride.
Antiviral Activity of 3-Methyleneoxindole
Authors: Tuli V. , Moyed H. S. , Stevenson D. , Gordon I.
Published: June 2012

3-Methyleneoxindole (MO), an oxidation product of the plant auxin indole-3-acetic acid, can selectively inhibit the replication of herpes-, mengo-, polioviruses, and Sindbis virus. The antiviral action of MO, a sulfhydryl binding compound, is neutralized by 2-mercaptoethanol if the latter is added soon after exposure of infected cells to MO. If addition of 2-mercaptoethanol is delayed, the antiviral action of MO appears to be irreversible. Data are presented which indicate that the antiviral action of MO is not mediated by interferon.
New Antibiotic Produced by Bacteria, 5-β-
d
-Xylofuranosylneamine
Authors: Horii Satoshi , Nogami Ikuo , Mizokami Nariakira , Arai Yoshiaki , Yoneda Masahiko
Published: June 2012

A new aminoglycoside antibiotic was isolated from the fermentation broths of two strains of
Bacillus
species. The antibiotic is active against gram-positive and some gram-negative bacteria, and its antimicrobial spectrum is similar to that of ribostamycin. The chemical structure was determined to be 5-β-
d
-xylofuranosylneamine, which is identical to the deacylated product obtained from butirosin A.
Antibiotic Produced by
Fusarium equiseti
NRRL 5537
Authors: Burmeister H. R. , Bennett G. A. , Vesonder R. F. , Hesseltine C. W.
Published: June 2012

Fusarium equiseti
NRRL 5537 grown on an autoclaved white corn grit medium for 3 to 4 weeks at room temperature produced a substance in excess of 5 g/kg of substrate that inhibited some gram-positive bacteria including mycobacteria. Most
Bacillus subtilis, Mycobacterium phlei
, and
Staphylococcus aureus
strains were inhibited when 1 μg of the antibiotic per ml was incorporated into the culture medium. Except for
Neisseria perflava
, gram-negative bacteria, yeasts, and molds were not inhibited by 128 μg/ml. The antibiotic was recovered as a white powder, had a melting point of 65 to 66 C, and had an intraperitoneal mean lethal dose in white mice of 63 mg/kg of body weight. In thin-layer chromatographic analysis the compound appeared as a single spot in two different solvent systems. Mass spectrometry determined that the molecular weight of the antibiotic was 373 with a molecular formula of C
22
H
31
NO
4
. Chemical microanalysis was in accord with the formula.
In Vitro Antiviral Activity of 6-Substituted 9-β-
d
-Ribofuranosylpurine 3′,5′-Cyclic Phosphates
Authors: Sidwell Robert W. , Huffman John H. , Allen Lois B. , Meyer Rich B. , Shuman Dennis A. , Simon Lionel N. , Robins Roland K.
Published: June 2012

A series of twelve recently synthesized 6-substituted derivatives of 9-β-
d
-ribofuranosylpurine 3′,5′-cyclic phosphate (RPcMP) were evaluated for in vitro antiviral activity, using inhibition of viral cytopathogenic effect as the primary parameter for evaluation. Inhibition of the development of intra- and extracellular virus titer was used as a secondary criterion with certain viruses. Five derivatives were considered to have significant antiviral activity. 6-Hydroxylamino-RPcMP was active against type 1 herpes simplex, cytomegalo-, and vaccinia viruses. 6-Thio-RPcMP was inhibitory to types 1 and 2 herpes simplex, cytomegalo-, vaccinia, and type 3 parainfluenza viruses. The 6-methylthio derivative was active against types 1 and 2 herpes simplex, cytomegalo-, and vaccinia viruses, and types 1A, 2, 8, and 13 rhinoviruses; alteration of this 6-substitution to 6-ethylthio or to 6-benzylthio weakened the herpes- and vaccinia virus activity of the compound, but each continued to have significant antirhinovirus activity. The effect of time of addition of 6-methylthio-RPcMP to type 1 herpes simplex virus-infected cells was determined; the compound was most active when added prior to the virus. Early removal of the compound from the infected cells markedly reduced its antiviral effectiveness.
Iododeoxyuridine and Herpesviral Encephalitis: Lack of Inhibitory Action Against Low-Grade Viral Replication
Authors: Plummer G. , Ingerson Ann P.
Published: June 2012

Equine herpesvirus 1 replicated in the brains of 2-week-old mice but did not produce fatal encephalitis; it thus simulated the majority of cases of herpes simplex encephalitis in man. This replication was not inhibited by iododeoxyuridine, although in tissue cultures the equine and human viruses were equally susceptible. The continued use of iododeoxyuridine for human encephalitis should be seriously questioned.
Transamidinase Activity of Hyphal Fractions of a Streptomycin-Producing
Streptomyces griseus
Strain and Enhancement of Enzyme Activity in a Nonproducing Mutant
Authors: Barabás Gy. , Szeszák F. , Szabó G.
Published: June 2012

The presence of transamidinase (TA-se) was demonstrated in
Streptomyces griseus
strain 45 which does not produce streptomycin (SM). This enzyme is involved in the biosynthesis of streptidine, a component of the SM molecule. TA-se is generally thought to be present only in SM-producing
Streptomyces
strains. The recent results are, however, in agreement with out previous data which showed the presence of streptidine in the isolated cell wall of SM-nonproducing strain 45. The TA-se activity of this strain is very low, but we were able to increase it by addition of arginine or by increasing the incubation with
myo
-inositol. The addition of these substances to the cultures of SM-nonproducing
S. griseus
strains, which hitherto were deficient in TA-se, may serve as a method for detecting the presence of this enzyme. In an incubation system in which the hyphae of an SM-producing strain of
S. griseus
had been blended and separated by density gradient centrifugation, certain hyphal fractions had been combined, and their SM production and TA-se activity had been measured, we were unable to find any close correlation between TA-se activity and SM-producing capacity. The hyphal fractions and their combination did not show strict parallelism between TA-se activity and the level of SM production.
Rapid Microassays for Clindamycin and Gentamicin When Present Together and the Effect of pH and of Each on the Antibacterial Activity of the Other
Authors: Sabath L. D. , Toftegaard Inge
Published: June 2012

Gentamicin was measured in the presence of clindamycin by using as the assay organism a strain of
Staphylococcus aureus
that was resistant to clindamycin; clindamycin was measured in the presence of gentamicin by using
Clostridium perfringens
as the assay organism. Both assays were in agar diffusion systems, were rapid (2 to 4 h), and had errors of less than 10%. Neither antibiotic antagonized or synergized with the other against a variety of organisms. The pK of clindamycin was 7.3, and the pK of gentamicin was 8.2. Gentamicin was 100 or more times as active in alkaline medium against both gram-positive and gram-negative organisms, but clindamycin showed a striking pH effect on activity only with gram-positive organisms.
Purification and Characterization of Syringacin 4-A, a Bacteriocin from
Pseudomonas syringae
4-A
Authors: Haag William L. , Vidaver Anne K.
Published: June 2012

Syringacin 4-A, a bacteriocin produced by
Pseudomonas syrinagae
4-A, was obtained by induction with ultraviolet irradiation or mitomycin C. Approximately 1,000-fold purification of the bacteriocin was achieved by manganous chloride precipitation, differential centrifugation, and chromatography on hydroxyapatite columns. The purified syngacin was homogeneous on hydroxyapatite columns and sucrose density gradients; it also sedimented as a single entity in the analytical ultracentrifuge. The buoyant density of purified syringacin in cesium chloride was 1.294 g/ml. The sedimentation coefficient was calculated as 120
S
, and the diffusion coefficient was 6.49 × 10
−8
cm
2
/s. The molecular weight was calculated as 1.6 × 10
7
from physical data and 1.7 × 10
7
from biological data. The syringacin was composed of about 88.4% protein, 8.5% arabinose, 2.2% galacturonic acid, and 0.7% glucosamine. Amino acid analysis indicated a predominance of leucine (12.1%), aspartic acid (12.2%), and glutamic acid (12.7%). The ultraviolet spectrum showed a maximum absorbance peak at 276 nm. The syringacin was heat and alcohol sensitive, but resistant to trypsin, chymotrypsin, carboxypeptidase, Pronase, protease, lysozyme, steapsin, deoxyribonuclease, and ribonuclease. Maximum pH stability was between 5 and 8. Crude bacteriocin was stable at room temperature for at least a year, and purified material was stable for at least 3 months at 4 C.
Combined Activity of Sulfamethoxazole, Trimethoprim, and Polymyxin B Against Gram-Negative Bacilli
Authors: Rosenblatt J. E. , Stewart P. R.
Published: June 2012

The activity of the three two-drug combinations of sulfamethoxazole (SMX), trimethoprim (TMP), and polymyxin B (PB) against 52 clinical isolates of gram-negative bacilli was studied by a “checkerboard” agar dilution method. The organisms studied included strains of
Enterobacter
spp.,
Klebsiella pneumoniae, Serratia marcescens, Providence, Proteus
, and
Pseudomonas aeruginosa
. The majority of these isolates were resistant to at least two of the three agents used in the combined studies and to the most commonly used antimicrobials. The TMP-PB combination demonstrated enhanced activity more frequently than the other two-drug combinations, showing synergism or addition in 85% of the combined studies; indifference or antagonism was also observed least frequently with TMP-PB. The great majority (83%) of
Enterobacter-Klebsiella-Serratia
isolates were susceptible to enhanced activity of all combinations.
Proteus-Providence
isolates were frequently susceptible (63%), but combined activity was indifferent or antagonistic against 60% of
P. aeruginosa
. Twelve isolates were selected for “killing-curve” assays in which an inoculum was incubated with SMX, TMP, and PB individually and in various two- and three-drug combinations. Surviving bacteria were counted at timed intervals over 24 h of incubation. The triple combination (SMX-TMP-PB) was synergistic against 9 of 12 isolates, whereas TMP-PB and SMX-PB showed synergism against 5 and 3 isolates, respectively. These data suggest that, although TMP-PB will often show enhanced activity against the gram-negative bacilli studied here, optimal antibacterial activity will be demonstrated when the three-drug combination is used.
Butirosin Compared with Gentamicin In Vitro and In Vivo
Authors: Heifetz C. L. , Chodubski J. A. , Pearson I. A. , Silverman C. A. , Fisher M. W.
Published: June 2012

Butirosin (BTN) (P. W. K. Woo, G. L. Coffey, H. W. Dion, S. A. Fusari, and G. D. Senos, U. S. Patent 3,541,078, 1970) is a new aminoglycoside antibiotic notably active against opportunist bacterial species within
Pseudomonas, Klebsiella, Enterobacter, Serratia
, and
Proteus
. Numerous comparative tests were carried out with BTN and gentamicin (GTM) in vitro and in experimental infections in mice. BTN was more active in Mueller-Hinton broth than in agar, but its activity was lessened at acid pH or under anaerobiosis, as has been observed with other aminoglycosides. In standard agar diffusion tests, inhibition zones greater than 12 mm around 30-μg BTN disks generally denoted susceptibility, equivalent to minimal inhibitory concentrations [Formula: see text] 25 μg/ml. Cross-resistance between BTN and GTM occurred in a variable manner, with a number of bacterial strains strongly resistant to GTM being moderately susceptible to BTN. In mice, after a single subcutaneous injection, absorption of both antibiotics was rapid, with peak serum levels occurring in 15 min; this was followed by rapid elimination with estimated serum half-lives of about 20 min for each. After peroral administration of high doses in mice, there was no appreciable absorption of BTN. Several tests were carried out to compare BTN and GTM with respect to minimal inhibitory concentrations in vitro, acute subcutaneous median mouse protective doses, peak serum levels at such doses, and the therapeutic ratios derived from acute median protective and lethal doses. Although GTM usually proved to be more potent antibacterially on a weight basis, observations on BTN indicated a superior effectiveness in terms of therapeutic ratios.
Antibiotic G-418, a New
Micromonospora
-Produced Aminoglycoside with Activity Against Protozoa and Helminths: Fermentation, Isolation, and Preliminary Characterization
Authors: Wagman G. H. , Testa R. T. , Marquez J. A. , Weinstein M. J.
Published: June 2012

Antibiotic G-418 is a new aminoglycoside produced as the major component by a new species of
Micromonospora, M. rhodorangea
NRRL 5326. The antibiotic is prepared by submerged fermentation in a soybean-dextrin medium. Antibiotic G-418 is adsorbed on a cationic-exchange resin and separated from other impurities by passing it down a Dowex (1 × 2) resin column. The antibiotic, which contains 2-deoxystreptamine, has broad-spectrum antibacterial activity and is highly active against protozoa, amoebae, tapeworm, and pinworm infections in mice. This report describes the taxonomy of the organism, and fermentation, isolation, and preliminary characterization of antibiotic G-418.
Antimicrobial Activity of the Volatile Oil of
Nigella sativa
Linneaus Seeds
Authors: Toama Mohamed A. , El-Alfy Taha S. , El-Fatatry Hamed M.
Published: June 2012

The antimicrobial activity of the volatile oil of
Nigella sativa
Linneaus seeds was studied. The antimicrobial principle has been isolated, identified as thymohydroquinone, and found to be active against gram-positive bacteria and yeasts.
New Antimicrobial Nitrofuran,
trans
-5-Amino-3-[2-(5-Nitro-2-Furyl)Vinyl]-Δ
2
-1,2,4-Oxadiazole: Antibacterial, Antifungal, and Antiprotozoal Activities In Vitro
Authors: Gadebusch H. H. , Basch H. I.
Published: June 2012

trans
-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-Δ
2
-1,2,4-oxadiazole, a new antimicrobial nitrofuran, has shown microbial activity in vitro against a wide range of bacteria and fungi, and against several protozoa. The antimicrobial activity of the nitrofuran is not significantly diminished in vitro in the presence of 50% human serum. The compound is not cross-resistant with a number of common antibiotics or synthetic antimicrobial agents; some cross-resistance with furazolidone is encountered. The development of resistance to the compound in vitro, when it occurs, is mixed, but is unrelated to increase in pathogenicity of the test organism.
In Vitro And In Vivo Activity of 5-Fluorocytosine on
Acanthamoeba
Authors: Stevens A. R. , O'Dell W. D.
Published: June 2012

The results of our studies indicated that the avirulent Neff strain of
Acanthamoeba
was more susceptible to the activity of the anti-metabolite 5-fluorocytosine (5-FC) than was the virulent A-1 strain or a mouse brain reisolate of this strain, designated A-3. Results of competition experiments in which cultures were exposed simultaneously to 5-FC and either uracil, thymidine, or both uracil and thymidine demonstrated that the drug was directed against both deoxyribonucleic acid and ribonucleic acid in the avirulent strain, whereas ribonucleic acid was mainly affected in the virulent amebas. Concentrations >10 μg of 5-FC per ml were amebicidal to the avirulent strain; lower concentrations of the drug, which only affected growth slightly, significantly impaired the capacity of the cells to spontaneously encyst in stationary-phase cultures. On the other hand, the virulent strains were capable of growing in the presence of 5-FC (40 μg/ml) after an initial period of susceptibility. After a few transfers in growth medium lacking the drug, 5-FC-treated virulent amebas exhibited growth parameters typical of untreated cells. However, after successive subcultures in drug-free medium, 5-FC-treated cells lost their resistance and were again susceptible to the drug. This result suggested that the capacity of the cells to develop resistance resulted from a drug-induced mechanism. Spontaneous encystment, which was normally minimal in stationary-phase A-1 or A-3 cultures, was enhanced in A-3 but not A-1 cultures treated with 5-FC (>30 μg/ml). Results obtained from experiments to determine the effectiveness of 5-FC in protecting mice experimentally infected with either A-1 or A-3 amebas indicated that the clinical usefulness of 5-FC may be limited by the capacity of the amebas to develop resistance.
Comparison of Enzymatic and Microbiological Gentamicin Assays
Authors: Smith Arnold L. , Waitz J. Allan , Smith David H. , Oden Edwin M. , Emerson Barbara B.
Published: June 2012

The correlation coefficient between the rapid enzymatic and the overnight microbiological assays for 211 urine and serum specimens was 0.96. The 95% confidence limits yielded a correlation coefficient between 0.92 and 0.98. Both methods tended to underestimate the amount of a gentamicin added to urine. When only serum samples were considered, the predicted value obtained from the linear regression analysis of either method was within 0.57 μg/ml 99% of the time. This high degree of positive correlation will permit safe rapid adjustment of individualized patient gentamicin dosages.
Activity of Tetracycline, Doxycycline, and Minocycline Against Methicillin-Susceptible and -Resistant Staphylococci
Authors: Minuth J. N. , Holmes T. M. , Musher D. M.
Published: June 2012

Tetracycline, doxycycline, and minocycline were evaluated for their antibacterial activity against methicillin-susceptible and -resistant isolates of
Staphylococcus
. At clinically achievable levels both doxycycline and minocycline were more active than tetracycline against methicillin-susceptible organisms. Tetracycline and doxycycline had no activity against methicillin-resistant staphylococci, whereas minocycline at 2 μg/ml inhibited six of 13 strains and, at 3 μg/ml, 10 of 13 strains.
Single-Dose Daily Gentamicin Therapy in Urinary Tract Infection
Authors: Labovitz Elizabeth , Levison Matthew E. , Kaye Donald
Published: June 2012

Patients with urinary tract infection were treated for 8 to 15 days with one daily intramuscular injection of 160 mg of gentamicin or 60 or 80 mg every 8 h. Ten of 11 patients treated with one injection daily were cured as compared with 8 of 10 patients treated with three injections daily. Urinary concentrations of gentamicin were 3.2 to 600 μg/ml in all 8-h collections in patients receiving one injection daily and were 22 to 440 μg/ml in all 8-h collections in patients receiving three injections daily. The group treated once daily demonstrated a significant but reversible increase in mean serum creatinine concentration and decrease in mean creatinine clearance during therapy as compared with no change in the group treated with three injections daily. Decreases in renal function were correlated with higher milligram per kilogram doses and higher 1-h serum concentrations.
Transferrable Resistance to Tobramycin in
Klebsiella pneumoniae
and
Enterobacter cloacae
Associated with Enzymatic Acetylation of Tobramycin
Authors: Minshew Barbara H. , Holmes Randall K. , Sanford Jay P. , Baxter Charles R.
Published: June 2012

Among gram-negative bacilli isolated from burn wound cultures, some strains of
Enterobacteriaceae
were resistant to tobramycin (minimal inhibitory concentration [MIC]≥ 20 μg/ml) but susceptible to gentamicin (MIC ≤ 5 μg/ml). One
Klebsiella pneumoniae
and two
Enterobacter cloacae
strains were selected for studies on their mechanisms of resistance to aminoglycoside antibiotics. Resistance to high concentrations of tobramycin (MICs of 25 to 50 μg/ml) was conjugally transferred to a susceptible
Escherichia coli
strain at rates of 1.2 × 10
−4
to 2.8 to 10
−4
per donor cell, suggesting that resistance is controlled by R factors. Resistances to tobramycin, kanamycin, and neomycin were cotransferred. Enzymatic activities were present that acetylated tobramycin, gentamicin, and kanamycin in osmotic lysates from the donor and transcipient strains. Enzymatic adenylylation of these aminoglycosides was not observed. The aminoglycoside-acetylating activities from
K. pneumoniae
and
E. cloacae
resembled kanamycin acetyltransferase (KAT) in their specificity for aminoglycoside substrates. Not all isolates of bacteria that produce KAT are resistant to tobramycin, but the factors that determine susceptibility or resistance to tobramycin in KAT-producing bacteria have not yet been established.
Use of Available Dosage Forms of Cephalexin in Clinical Comparison with Phenoxymethyl Penicillin and Benzathine Penicillin in the Treatment of Streptococcal Pharyngitis in Children
Authors: Matsen John M. , Torstenson Ordean , Siegel Stuart E. , Bacaner Hadassah
Published: June 2012

The effectiveness of cephalexin, an oral cephalosporin using a dosage equivalent to available capsular dosage forms, was studied in relation to the effectiveness of phenoxymethyl penicillin and benzathine penicillin in the treatment of 128 patients with beta-hemolytic streptococcal pharyngitis, all but six of whom had group A streptococci isolated from throat cultures. Approximately one-half, 66 patients, received cephalexin for 10 days; 34 patients received phenoxymethyl penicillin for 10 days; and 28 patients had a single injection of benzathine penicillin. There were four treatment failures determined bacteriologically post-therapy, two in the cephalexin treatment group and one each in the oral penicillin and intramuscular penicillin groups. Similar cure rates of 96.7, 97.1, and 96.4% were computed for the respective treatment regimens. Whereas intramuscular benzathine penicillin remains the regimen of choice in most instances, cephalexin appeared to be as effective as oral penicillin in the elimination of group A streptococci from the pharynx when oral treatment was desired for streptococcal pharyngitis.
Inhibition of Herpesvirus Replication by Marine Algae Extracts
Authors: Deig E. Frank , Ehresmann Douglas W. , Hatch Melvin T. , Riedlinger Delimar J.
Published: June 2012

Extracts from two species of marine red algae,
Cryptosyphonia woodii
and
Farlowia mollis
, specifically inhibited herpes simplex virus replication in vitro.
Clinical Pharmacology of Pivampicillin
Authors: Roholt K. , Nielsen B. , Kristensen E.
Published: June 2012

Studies on pivampicillin hydrochloride and ampicillin trihydrate, administered in capsules to healthy volunteers, indicated that pivampicillin was absorbed more efficiently from the gastrointestinal tract than ampicillin. Average peak concentrations of ampicillin in the serum after doses equimolar to 250 mg of ampicillin were 6.8 μg/ml at 56 min with pivampicillin and 1.96 μg/ml at 1 h 24 min with ampicillin. The maximal concentration after pivampicillin treatment was also higher than that recorded when twice the equimolar dose of ampicillin, which averaged 3.2 μg/ml at 1 h 42 min, was used. The urinary excretion of ampicillin, expressed as a percentage of the administered dose, averaged 67 to 73 and 25 to 29% after administration of pivampicillin and ampicillin, respectively. The bioavailability of ampicillin, taken as the area under the serum curve, obtained with pivampicillin at a 250-mg ampicillin dose level was superior to that obtained with a 500-mg dose of ampicillin. Comparison of a suspension intended for children, containing the pivampicillin free base with a suspension of ampicillin trihydrate, emphasized the difference recorded for the capsule preparations. Administration of pivampicillin with a meal rich in fat and protein had no depressant effect on the absorption. Concurrent administration of probenecid caused higher and prolonged concentrations of ampicillin in the serum.
Triple Crossover Study on Absorption and Excretion of Ampicillin, Pivampicillin, and Amoxycillin
Authors: Verbist L.
Published: June 2012

The absorption and excretion of equivalent doses of ampicillin, pivampicillin, and amoxycillin were compared in 10 healthy volunteers after administration of these antibiotics in a randomized triple crossover fashion. As recommended, ampicillin and amoxycillin were administered on an empty stomach, whereas pivampicillin was given with breakfast. The mean half-life times were nearly identical for all three antibiotics: 60.9 min for ampicillin; 58.4 min for pivampicillin; and 62.2 min for amoxycillin. The absorption of the drugs was evaluated according to the following three criteria: the mean peak serum levels; the “area under the curve”; and the percentage of recovery in urine. By these criteria, pivampicillin was the best-absorbed drug, with absorption 3.0 to 3.6 times higher than that of ampicillin and 1.2 to 1.5 times higher than that of amoxycillin, whereas the absorption of amoxycillin was 2.1 to 2.9 times higher than that of ampicillin.
Effect of Adenosine Deaminase upon the Antiviral Activity In Vitro of Adenine Arabinoside for Vaccinia Virus
Authors: Connor James D. , Sweetman Lawrence , Carey Sharen , Stuckey Margaret A. , Buchanan Robert
Published: June 2012

This study determined that the effect of 9-β-
d
-arabinofuranosyl-adenine (adenine arabinoside, Ara-A) upon vaccinia virus plaque development in the stable monkey kidney line, LLC-MK
2
, was increased approximately 40-fold when an inhibitor of adenosine deaminase (ADA) was added to the tissue culture media along with infective inocula. The concentration of Ara-A required to completely suppress plaque development (total plaque inhibitory concentration
100
; TPIC
100
) was greater than 10 μg/ml. However, when ADA activity was inhibited, the TPIC
100
was 0.5 μg/ml or less. Chromatographic assay of arabinosylpurines in the media provided evidence that adenine arabinoside was rapidly deaminated to 9-β-
d
-arabinofuranosylhypoxanthine by the cellular monolayers, in the absence of animal serum, and that the rate of deamination, at 5 μg/ml, by the cells was equal to the rate of diffusion of Ara-A across the cellular membrane. The half-life of Ara-A in the media, starting with 5 μg/ml, was 2 to 3 h and shorter at lower concentrations. The study demonstrates the profound effect that an indicator system, acting as an intact biological unit, can have upon a potential antiviral compound.
Mutagenic Activity of Diazoacetylglycine Derivatives
Authors: Monti-Bragadin C. , Tamaro M. , Banfi E.
Published: June 2012

Some diazoacetyl derivatives of glycine known as antitumor and immunosuppressive agents have been found to be powerful mutagens of the base substitution type.
Pharmacokinetics of Metronidazole as Determined by Bioassay
Authors: Ralph Edward D. , Clarke John T. , Libke Robert D. , Luthy Ruedi P. , Kirby William M. M.
Published: June 2012

The pharmacokinetics of metronidazole, a drug effective in vitro against most anaerobic bacteria and promising in treating anaerobic infections, are described. Serum and urine levels after single and multiple doses in 10 adult male volunteers were measured by an agar well diffusion bioassay using clostridial species as the test organisms under anaerobic conditions. Peak serum levels averaged 11.5 μg/ml and 6.2 μg/ml after single 500-mg and 250-mg doses, respectively. Renal clearance was only 10.2 ml/min per 1.73 m
2
, and less than 20% of the administered dose was recovered in the urine as active drug in 24 h. The average serum half-life was 8.7 h, and there was no protein binding as determined by an ultrafiltration method. With multiple doses of metronidazole (500 mg four times a day and 250 mg three times a day), blood levels increased progressively for the first few doses and then leveled off, with no significant accumulation occurring between 3 and 7 days. On 250 mg three times a day, serum levels just before the 8 a.m. dose (12 h after the preceding dose) on the third day averaged 3.9 μg/ml, and before the 8 p.m. dose, 5.7 μg/ml. For the higher, 500-mg dose (four times a day) regimen, the corresponding minimum serum levels were 13.1 μg/ml at 8 a.m. and 21.3 μg/ml at 8 p.m. Peak levels would have been about 10 μg/ml higher, and since the minimum inhibitory concentrations of most anaerobes including
Bacteroides fragilis
are less than 6 μg/ml, these concentrations should be highly effective therapeutically, even for severe infections.
Continuous Non-Therapeutic Use of Antibacterial Drugs in Feed and Drug Resistance of the Gram-Negative Enteric Florae of Food-Producing Animals
Authors: Siegel D. , Huber W. G. , Enloe F.
Published: June 2012

Fecal samples from Illinois farm animals and Montana range cattle were examined for the frequency of gram-negative enteric organisms resistant to oxytetracycline, dihydrostreptomycin, or ampicillin. The Illinois farm animals were continually fed rations containing various antibacterial drugs. The Montana range cattle had minimal exposure to antibacterial drugs. The majority of samples from Illinois farm animals demonstrated 10% or more antibiotic-resistant organisms. In contrast, resistant organisms could not be detected in the majority of samples from Montana range cattle. The majority of
Escherichia coli
isolated from Illinois farm animals was resistant to various antibacterial drugs, whereas less than 1.6% of the isolates from Montana range cattle were resistant to any one of the antibacterial drugs tested.
On the Mechanism of Action of Vancomycin: Inhibition of Peptidoglycan Synthesis in
Gaffkya homari
Authors: Hammes Walter P. , Neuhaus Francis C.
Published: June 2012

Vancomycin inhibits the synthesis of peptidoglycan in membrane preparations from
Gaffkya homari
with uridine diphosphate-
N
-acetylmuramyl (UDP-Mur-NAc)-pentapeptide as substrate, but not with either UDP-MurNAc-tetrapeptide or UDP-MurNAc-tripeptide. These results are correlated with the specificity studies described by Perkins and Nieto for complex formation between the antibiotic and the peptide subunit. It is concluded that the formation of a complex between vancomycin and a postulated cell wall acceptor or between vancomycin and the enzymes involved in peptidoglycan synthesis does not contribute to the inhibitory action of this antibiotic. The mechanism of vancomycin action on peptidoglycan synthesis is clearly different from that of moenomycin and bacitracin. In the presence of these antibiotics, peptidoglycan synthesis is inhibited with both UDP-MurNAc-pentapeptide and -tetrapeptide as substrates. In addition, these results provide additional insight into the mechanism of phospho-MurNAc-pentapeptide translocase. For example, enhancement of the transfer of phospho-MurNAc-peptide from UDP-MurNAc-peptide to undecaprenyl-phosphate at low concentrations of vancomycin is observed with UDP-MurNAc-pentapeptide and not with -tetrapeptide. Complexation of vancomycin with undecaprenyl-diphosphate-MurNAc-pentapeptide, resulting in an ineffective intermediate, would increase the rate of transfer by preventing the reassociation of undecaprenyl-diphosphate-MurNAc-pentapeptide with the enzyme.
Characterization and Prevalence of the Different Mechanisms of Resistance to Beta-Lactam Antibiotics in Clinical Isolates of
Escherichia coli
Authors: Medeiros Antone A. , Kent Ralph L. , O'Brien Thomas F.
Published: June 2012

A survey of clinical isolates from a hospital laboratory showed that
Escherichia coli
could be grouped into three classes of beta-lactam-antibiotic resistance by results of routine susceptibility testing to ampicillin, cephalothin, and carbenicillin.
E. coli
highly resistant to ampicillin and carbenicillin but not to cephalothin (class I) were found to have one of two levels of R factor-mediated, periplasmic-β-lactamase which resembled R
TEM
and was located behind a permeability barrier to penicillins but not to cephalosporins. This permeability barrier appeared to act synergistically with the β-lactamase in producing high levels of resistance to penicillins.
E. coli
highly resistant to ampicillin and cephalothin but not carbenicillin (class II) were found to have a β-lactamase with predominantly cephalosporinase activity which was neither transferable nor releasable by osmotic shock.
E. coli
moderately resistant to one or to all three of these antibiotics (class III) were found to have low levels of different β-lactamases including a transferable β-lactamase which resembled R
1818
. Thus, different mechanisms producing resistance to β-lactam antibiotics could be deduced from the patterns of resistance to ampicillin, cephalothin, and carbenicillin found on routine susceptibility testing.
E. coli
of class I were much more prevalent than the other classes and the proportion of
E. coli
that were class I increased with duration of patient hospitalization. The incidence of class I
E. coli
rose only slightly over the past 7 years and that of class II
E. coli
remained constant despite increased usage of both cephalothin and ampicillin. These observations emphasize that the properties of the apparently limited number of individual resistance mechanisms that exist in a bacterial flora, such as their genetic mobility and linkages and the spectrum of their antibiotic inactivating enzymes and permeability barriers, may govern the effect that usage of an antibiotic has upon the prevalence of resistance to it and to other antibiotics.