bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Contributing to Resistance to Beta-Lactam Antibiotics in
Bacteroides fragilis
Authors: Olsson Barbro , Dornbusch Kathrine , Nord Carl Erik
Published: June 2012

Fifteen strains of
Bacteroides fragilis
, five highly resistant, five moderately resistant, and five susceptible to benzylpenicillin and cephaloridine, were tested for β-lactamase production. In the highly resistant and the moderately resistant groups of strains, a correlation between formation of β-lactamase and minimal inhibitory concentrations was demonstrated. In the presence of the β-lactamase inhibitors clavulanic acid and CP-45,899 at concentrations of 1 μg/ml, the susceptibility to cephaloridine increased fourfold or more in the β-lactamase-producing strains. Crypticity measurements (β-lactamase activity broken/intact cells) with cephaloridine as substrate could indicate a diffusion barrier in the cell wall.
Conditional Antifolate Resistance in
Bacillus subtilis thyA
Authors: Farmer James L.
Published: June 2012

Resistance to antifolates in
Bacillus subtilis
strains results from the presence of an antifolate resistance mutation (
afo
). Strains which are
thyA
+
afo
are unconditionally resistant to antifolates. The conditional resistance of
thyA afo
strains is hypothesized to be due to the
thyB
+
gene product (thymidylate synthetase B) having a high

K
m

for the folate substrate, thus leading to thymineless death in the presence of antifolates. An alternative model for conditional antifolate resistance was shown to be incorrect by analysis of folate metabolism in methotrexate-treated cells. Genetic analysis and studies of the response of
afo
+
cells to methotrexate suggested that most, if not all,
B. subtilis
thymine-requiring mutants are
afo
. Analysis of dihydrofolate reductase from
afo
cells did not reveal an obvious mechanism for antifolate resistance in those cells.
Biosynthesis of Kitasamycin(Leucomycin) by Leucine Analog-Resistant Mutants of
Streptomyces kitasatoensis
Authors: Vézina Claude , Bolduc Cécile , Kudelsk Alicia , Audet Pierre
Published: June 2012

The biosynthesis of kitasamycin in
Streptomyces kitasatoensis
B-896 was profoundly influenced by the addition of precursors to complex and defined media:
l
-valine and
l
-leucine directed biosynthesis towards the pairs A
4
/A
5
(R
2
= butyryl) and A
1
/A
3
(R
2
= isovaleryl), respectively, and total kitasamycin titers were doubled and quadrupled, respectively.
S. kitasatoensis
B-896 was very resistant (>20 mg/ml) to α-aminobutyric acid, an analog of
l
-valine, but very susceptible to
l
-leucine analogs 5′, 5′, 5′-trifluoroleucine and 4-azaleucine (5 to 10 μg/ml). The inhibition by 4-azaleucine could be reversed by
l
-leucine, but by none of the other amino acids of the pyruvate family or the amino acids of the aspartate pathway. 4-Azaleucine-resistant mutants were isolated which in the absence of any precursors overproduced
l
-leucine and a kitasamycin complex mainly consisting of the pair A
1
/A
3
. These 4-azaleucine-resistant mutants are presumed to be regulatory mutants in which α-isopropylmalate synthase, the first enzyme of the
l
-leucine pathway, has become either derepressed or desensitized to leucine feedback inhibition.
l
-Leucine-regulatory mutants have economic value: in the absence of expensive precursors, they produce a kitasamycin complex in which the most potent pair A
1
/A
3
is dominant and the least active components are absent.
Effects of Dextranases on Attachment of
Streptococcus mutans
to Hydroxyapatite
Authors: Simonson L. G. , Jackola D.
Published: June 2012

A
Fusarium
dextranase and a
Penicillium
dextranase were compared for their relative ability to quantitatively reduce the adsorption of
3
H-labeled
Steptococcus mutans
cells onto hydroxyapatite.
Fusarium
dextranase-treated hydroxyapatite disks caused a statistically significant decrease in the hydroxyapatite adsorption of both the OMZ 176 and NCTC 10449 strains of
S. mutans
relative to untreated control disks. The extent of initial bacterial adsorption was not promoted by sucrose-dependent glucan synthesis. Since the
Fusarium
dextranase has a much greater affinity for hydroxyapatite than the
Penicillium
dextranase, it could represent an enzyme with improved decay-preventive therapeutic properties. This was concluded because the
Fusarium
dextranase may interfere with both the initial attachment and later glucan-dependent accumulation of dental plaque microorganisms.
Isolation and nature of intracellular alpha-aminoadipic acid-containing peptides from Paecilomyces persicinus P-10
Authors: Eriquez L A , Pisano M A
Published: June 2012

Small intracellular peptides containing alpha-aminoadipic acid, cysteine, and a valine moiety were obtained from mycelia of Paecilomyces persicinus P-10 by ethanol or trichloroacetic acid extraction. After performic acid oxidation and ion-exchange chromatography, analysis of the peptide fractions by two-dimensional thin-layer electrophoresis and chromatography revealed the presence of three related peptides, as sulfonic acid derivatives, each containing alpha-aminoadipic acid. Each peptide was isolated in chromatographically pure form by semipreparative thin-layer electrophoresis and chromatography. The purified peptides were subjected to differential hydrolysis, dansylation, and combined dansylation-phenylisothiocyanate sequence analysis. Based on these studies, the structures of the isolated peptides were determined to be (i) glycl-delta-(alpha-aminoadipyl)-cysteinyl-beta-hydroxyvaline, (ii) glycyl-delta-(alpha-aminoadipyl)-cysteinylvaline, and (iii) delta-(alpha-aminoadipyl)-cysteinylvaline. The peptides isolated from Paecilomyces are similar to the alpha-aminoadipic acid-cysteine-valine moiety complex peptides isolated from Cephalosporium.
Effect of Divalent Cation Concentrations on the Antibiotic Susceptibilities of Nonfermenters Other than
Pseudomonas aeruginosa
Authors: Fass Robert J. , Barnishan Jean
Published: June 2012

The effects of supplementing Mueller-Hinton broth with calcium and magnesium on the minimal inhibitory concentrations (MICs) of eight aminoglycosides, colistin, tetracycline, and carbenicillin for 11 nonfermenters other than
Pseudomonas aeruginosa
were studied and compared with the effects for
Escherichia coli
and
P. aeruginosa
. MICs were simultaneously performed in unsupplemented Mueller-Hinton broth and Mueller-Hinton broth supplemented to contain 5 mg of calcium and 2.5 mg of magnesium per dl. Changes in MICs were expressed as the increases in the number of log
2
concentrations caused by supplementation. The usual increases in MICs of aminoglycosides caused by supplementation were: zero concentrations for
E. coli
, one to six concentrations for
P. aeruginosa
, and one to two concentrations for most other nonfermenters. The largest increases (five to six concentrations) were observed with gentamicin and
P. aeruginosa
. The usual increases in MICs of colistin were: zero concentrations for
E. coli
, two concentrations for
P. aeruginosa
, and one to two concentrations for other nonfermenters. Increases in MICs of tetracycline were: one to five concentrations for all organisms tested. The usual increases in MICs of carbenicillin were: zero concentrations for
E. coli
and
P. aeruginosa
and zero to two concentrations for other nonfermenters. These observations indicated that supplementation of Mueller-Hinton broth to contain recommended concentrations of calcium and magnesium had little effect on MICs of aminoglycosides and colistin for
E. coli
but increased MICs for most nonfermenters, increased MICs of tetracycline for
E. coli
and all nonfermenters, and had little effect on MICs of carbenicillin for
E. coli
and
P. aeruginosa
but increased the MICs for several nonfermenters other than
P. aeruginosa
.
Compounds affecting membranes that inhibit protein synthesis in yeast
Authors: Alonso M A , Vázquez D , Carrasco L
Published: June 2012

The regulation of translation has been investigated in yeast cells by means of ionophores and other compounds affecting the ionic concentration inside the cell. Treatment of a variety of cells with these compounds produces a drastic inhibition in the protein-synthesizing activity of the cell. Protein synthesis in yeast is strongly inhibited by amphotericin B and nystatin. Mammalian cells are blocked in their translation capacity by gramicidin D, nigericin, monensin, nystatin, A23187, and bromolasalocid. The effects of these compounds on protein synthesis in Escherichia coli and Staphylococcus aureus were also investigated. Amphotericin B is a powerful inhibitor of both protein and ribonucleic acid syntheses in yeast cells at concentrations that do not affect the transport of the labeled amino acid or nucleoside precursor. The analysis of the polysomal profiles in yeast spheroplasts could indicate that initiation is the target of amphotericin B action on translation. Studies on the reversion of the protein synthesis blockade by amphotericin B by increasing the potassium concentration in the medium suggest that changes in the potassium concentration in cellular cytoplasm might be responsible, at least in part, for the inhibition of protein synthesis.
Ampicillin and Tetracycline in the Treatment and Prophylaxis of Chronic Bronchitis
Authors: Hahn H. H. , MacGregor R. R. , Avent C. K. , Counts G. W. , Smith H. E. , Beaty H. N.
Published: June 2012

Ampicillin and tetracycline, in doses of 2 g a day, were compared in the treatment of acute exacerbations of chronic bronchitis. Seventy-nine patients were followed for 3 to 29 months and were treated for 118 exacerbations. Clinical improvement occurred after 10 days of treatment with either drug in over 80% of the cases.
Haemophilus influenzae
and
Diplococcus pneumoniae
were eradicated from the sputum more than 60% of the time, but in general there was a poor correlation between bacteriological clearing and clinical response. The effect of chemoprophylaxis with ampicillin and tetracycline in doses of 1 g a day on the frequency of acute exacerbations of bronchitis was compared with that of a placebo. Seven hundred eighty prophylactic regimens, consisting of one capsule every 12 hr for 5 days beginning with the first sign of a cold, were prescribed for 76 patients. Irrespective of the regimen, an acute exacerbation of bronchitis was encountered at approximately 13% of the follow-up visits to the clinic.
New Method for Antibiotic Susceptibility Testing
Authors: Rolinson G. N. , Russell Elizabeth J.
Published: June 2012

The most widely used method for routine antibiotic susceptibility testing of clinical isolates of bacteria is the paper-disc method. This has the advantage of simplicity, but to obtain reliable results considerable care is required both in the standardization of the procedure and in the interpretation of the zones of inhibition. A new susceptibility test method is described in this report which retains the simplicity of the paper-disc method but which enables organisms to be tested directly for susceptibility to known concentrations of antibiotic in agar. Organisms may be tested against a single concentration of antibiotic or, alternatively, a range of concentrations may be used to determine the minimal inhibitory concentration. The method utilizes stable pre-prepared materials and is not appreciably more time consuming than the conventional disc method.
Bactericidal and Sporicidal Activity of a Quaternary Ammonium Resin-Triiodide Complex
Authors: Gilmour Marion N. , Wicksell Eva K.
Published: June 2012

Tests to determine the potential use of a quaternary ammonium resin-triiodide complex as a sterilizing agent showed that it was an ineffective sporicide and that bactericidal activity was impaired by complex milieu.
Relationship Between the Uptake of Isoniazid and Its Action on In Vivo Mycolic Acid Synthesis in
Mycobacterium tuberculosis
Authors: Wang Lynn , Takayama Kuni
Published: June 2012

A direct relationship was established between the rate of uptake of isoniazid and the action of this drug on in vivo mycolic acid synthesis in
Mycobacterium tuberculosis
H37Ra. The rate of uptake of isoniazid increased linearly with its external concentration and appeared to reach a maximal value of 52 pmoles per hr per 10
9
cells at an external concentration of about 13 μ
m
. Correspondingly, the rate of inhibition of mycolic acid synthesis increased with the rise in the rate of uptake of the drug. A 50% inhibition of mycolic acid synthesis occurred when the uptake of isoniazid reached 5.2 pmoles per 10
9
cells. Calculations showed that this level of drug uptake represents an internal cellular concentration of 9 μ
m
. These results show clearly that the action of isoniazid on the mycolate synthetase system of
M. tuberculosis
is rapid and that this enzyme system is highly sensitive to the drug.
Dual Effect in the Mechanism of Action of Anti-Influenza Virus Amino Acid Analogues
Authors: Fujita Haruhisa
Published: June 2012

In comparative research studies to clarify the mechanism governing the effects of anti-influenza amino acid analogues, it was established that amino acid analogues exhibit definite chemotherapeutic properties. They possess dual activity capable of inhibiting multiplication and pulmonary consolidation induced by influenza virus infection.
dd
-Carboxypeptidase-Transpeptidase and Killing Site of β-Lactam Antibiotics in
Streptomyces
Strains R39, R61, and K11
Authors: Dusart Jean , Marquet Alberto , Ghuysen Jean-Marie , Frère Jean-Marie , Moreno Ramon , Leyh-Bouille Melina , Johnson Kenneth , Lucchi Chantal , Perkins Harold R. , Nieto Manuel
Published: June 2012

Additional evidence is given that in
Streptomyces
strains R39, R61, and K11 the same enzyme performs
dd
-carboxypeptidase and transpeptidase activities and that this enzyme is the killing site of β-lactam antibiotics. With strain R61, it was found that the exocellular enzyme has a sensitivity towards some antibiotics different from that of the membrane-bound enzyme. Under the growth conditions used in the present investigations, β-lactamase activity was not involved in susceptibility to β-lactam antibiotics.
Pharmacokinetic Studies of Tobramycin and Gentamicin
Authors: Simon V. K. , Mösinger E. U. , Malerczy V.
Published: June 2012

Broth dilution susceptibility tests of 100 isolates of
Pseudomonas aeruginosa
and 101 isolates of
Staphylococcus aureus
against tobramycin (formerly nebramycin factor 6) and gentamicin showed that tobramycin was more effective against
P. aeruginosa
and less effective against
S. aureus
. The minimal inhibitory concentration of tobramycin against the
Pseudomonas
sp. isolates that required 5 μg of gentamicin per ml for inhibition ranged from 0.63 to 0.31 μg/ml. Peak concentrations in the blood of 10 healthy adults after intramuscular injection of 80 and 40 mg of tobramycin averaged 3.7 ± 0.62 and 2.4 ± 0.27 μg/ml, and declined to 0.56 ± 0.05 and 0.26 ± 0.02 μg/ml, respectively, after 6 h. The urine recovery averaged 60%. The half-life was 1.6 h. During continuous intravenous infusion of tobramycin and gentamicin (infusion rate 6.6 mg per h), blood levels at steady state were 0.94 ± 0.10 and 1.04 ± 0.06 μg/ml, respectively. For both antibiotics, the calculated distribution volume ranged from 15 to 17 liters. The renal clearance to tobramycin averaged 76% and that of gentamicin averaged 85% of the total clearance, indicating that the drugs are primarily eliminated by the kidneys. The present results suggest that tobramycin may be more successful in the treatment of
Pseudomonas
infections than gentamicin at the same dosage (80 mg intramuscularly three to four times daily).
Simplified Assay for Gentamicin in the Presence of Other Antibiotics
Authors: Alcid David V. , Seligman Stephen J.
Published: June 2012

Gentamicin concentration was estimated by using a clinical isolate of a multiple antibiotic-resistant strain of
Staphylococcus epidermidis
in an agar well diffusion assay. The presence of clinically attainable concentrations of cephalothin, ampicillin, carbenicillin, clindamycin, or chloramphenicol did not affect the assay.
Biosynthetic studies on antibiotic A47934
Authors: Zmijewski M J , Briggs B , Logan R , Boeck L D
Published: June 2012

A47934, a peptide antibiotic produced by Streptomyces toyocaensis, belongs to the glycopeptide class of compounds which includes ristocetin and vancomycin. Incorporation studies with radioisotope-labeled substrates indicated that tyrosine, p-hydroxyphenylglycine, p-hydroxyphenylglyoxylate, acetate, and sulfate were efficiently incorporated into A47934. This is consistent with the reported biosynthesis of other glycopeptide antibiotics. Prototrophic mutants blocked in antibiotic biosynthesis were isolated at a low frequency (0.4%) after mutagenesis. Secretor-convertor pairings of the 36 mutants obtained demonstrated that they belonged to three classes: two groups of secretor-convertor pairs and a larger group of mutants that did not make antibiotic under any condition tested. Neither the secretor-convertor studies not supplementation of the cultures with putative biosynthetic intermediates was useful in identifying the location of the biosynthetic blocks. All studies to determine the timing of the sulfate addition step in the biosynthesis indicated that the sulfate is added prior to the formation of intermediates that possess antimicrobial activity.
SCH 39304 in the treatment of acute or established murine pulmonary blastomycosis
Authors: Brummer E , Hanson L H , Stevens D A
Published: June 2012

SCH 39304 was tested for treatment of acute or established murine pulmonary blastomycosis and was compared with ketoconazole and fluconazole in a model of acute infection. Only SCH 39304 at 25 or 50 mg/kg of body weight per day produced 100% survival for 30 days after the 20-day treatment, although only 33% of the mice were cleared of infection. SCH 39304 at 2 mg/kg/day was similar to ketoconazole at 100 mg/kg/day and to fluconazole at 10 mg/kg/day. In a model of established blastomycosis, used to evaluate long-term treatment of very sick or moribund mice, SCH 39304 at 50 mg/kg/day protected against death with a 96% cumulative 8-week survival. SCH 39304 was clearly superior on a milligram-per-kilogram basis in acute blastomycosis, and long-term treatment of more severe blastomycosis was curative.
In vitro susceptibilities of the Bacteroides fragilis group to 14 antimicrobial agents in Korea
Authors: Lee K , Jang I H , Kim Y J , Chong Y
Published: June 2012

The susceptibilities to 14 antimicrobial agents of 172 clinical isolates of the Bacteroides fragilis group from Korean patients during 1989 and 1990 were tested by an agar dilution method. All the isolates tested were susceptible to imipenem, chloramphenicol, and metronidazole. The rate of resistance to cefoxitin was 6%.
Activities of antifolate, antiviral, and other drugs in an immunosuppressed rat model of Pneumocystis carinii pneumonia
Authors: Walzer P D , Foy J , Steele P , Kim C K , White M , Klein R S , Otter B A , Allegra C
Published: June 2012

The efficacy of antifolate, antiviral, and other drugs was compared in an experimental model of pneumocystosis. Sulfamethoxazole (SMX) administered alone in doses of greater than or equal to 60 mg/kg/day was highly effective in treatment and prophylaxis. Low (less than or equal to 15 mg/kg/day) doses of SMX showed limited, dose-related anti-Pneumocystis carinii activity in therapy but were more effective in prophylaxis. The dihydrofolate reductase (DHFR) inhibitors trimethoprim (TMP), pyrimethamine, and trimetrexate exhibited little anti-P. carinii activity when administered alone and did not enhance the efficacy of SMX; the effects of the DHFR inhibitors could not be related to the dose or the concentration in serum. These data suggested that the rat model is an excellent system for studying the anti-P. carinii activity of sulfonamides but is of limited value in studying DHFR inhibitors. The antiviral drugs azidothymidine, dideoxyinosine, inosine pranobex (Isoprinosine), amantadine, and acyclovir displayed little or no activity against P. carinii; however, azidothymidine did not impair the efficacy of SMX or TMP-SMX. These results supported the clinical practice of giving antiviral agents together with antifolate drugs to patients infected with human immunodeficiency virus and suggested that the beneficial effects of antiviral agents on the occurrence of pneumocystosis are due mainly to their effects on the virus or the host immune response. In contrast to the antiviral drugs, 9-deazainosine, a nucleoside analog with antiprotozoal properties, demonstrated marked activity against P. carinii which was related to dose and route of administration. These data raised the possibility that anti-P. carinii activity is a general property of purine nucleosides and suggested that further exploration of this class of compounds might lead to clinically useful agents.
Topical treatment of infection with acyclovir-resistant mucocutaneous herpes simplex virus with the ribonucleotide reductase inhibitor 348U87 in combination with acyclovir
Authors: Safrin S , Schacker T , Delehanty J , Hill E , Corey L
Published: June 2012

The thiocarbonohydrazone 348U87 inactivates herpes simplex virus ribonucleotide reductase and potentiates the activity of acyclovir against wild-type and acyclovir-resistant strains of herpes simplex virus. We treated 10 human immunodeficiency virus-infected patients with acyclovir-resistant anogenital herpes simplex virus infection with a topical preparation of 348U87 (3%) in combination with acyclovir (5%) in an open-labelled study. Transient improvement with combination therapy occurred frequently; however, target lesions reepithelialized completely in only 1 of 10 patients. Termination of study drug therapy was most often due to cessation of therapeutic effect before complete resolution of lesions. As currently formulated, topical 348U87 offers little therapeutic benefit for this indication.
Screening Method of Agents Against the R Factor by the Use of an Hfr Made by Integrative Suppression with an R Factory
Authors: Yoshikawa Masanosuke
Published: June 2012

By the use of an Hfr strain made by integrative suppression of a derepressed R factor, R100-1 in a
dnaA
-ts mutant of
Escherichia coli
and several other appropriate control strains with and without the R factor, a screening system was established which can be used to detect agents which are either inhibitory to the replication of the R factor and lead to its “curing” or are preferentially inhibitory to the growth of the R-carrying bacteria. The validity of this system was shown with several agents already known to be experimentally effective.
Rapid Disk Test for Determining Clindamycin Serum Levels
Authors: Liberman Daniel F. , Fitzgerald Jude , Robertson Richard G.
Published: June 2012

A disk bioassay for determining clindamycin serum levels is presented. This method is rapid (results available in 6.0 to 6.5 h), reliable, and simple to perform.
Isolation, Characterization, and Action of Colicin M
Authors: Braun Volkmar , Schaller Klaus , Wabl Matthias R.
Published: June 2012

Colicin M was isolated from
Escherichia coli
K-12 32T 19F/T1. The purified, biologically active protein had a molecular weight of 27,000. It contained phosphatidyl ethanolamine. The molecular weight found for the polypeptide chain by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate was 18,000. Colicin M was found to be firmly integrated in the membrane of the producing strain. The action of the colicin seems to be on the membrane, since cells of the susceptible strain
E. coli
K-12 ROW/V/22.1 lyse rapidly. Using the phase contrast microscope, lysis was followed by decrease in turbidity of the cell culture and release of protein into the medium. Lysis started at about 15 min after addition of colicin M and was completed after 40 to 60 min. At this time, one-third of the protein had been released from the cells. The number of viable cells dropped within 10 min to 0.01%. Colicin M induced formation of spheroplasts in the presence of 16% sucrose. The electron microscope examination revealed that at first bulges in the cell envelope appear, most frequently occurring equatorially but also occurring at sites all over the cell. In the process of spheroplast formation, the cytoplasmic membrane often retreats from one-half of the outer membrane so that the cytoplasm is confined to one hemisphere. Sucrose did not prevent cells from dying unless cells were pregrown in a sucrose containing medium for several generations before colicin M was added. With cells pregrown in the presence of sucrose, the number of survivors was 100 times higher than in the absence of sucrose.
Demonstration of R Factors From
Pseudomonas aeruginosa
Authors: Iyobe Shizuko , Hasuda Katsumi , Fuse Aisaku , Mitsuhashi Susumu
Published: June 2012

Sixty strains of
Pseudomonas aeruginosa
were selected from our clinical stock cultures and used as donors of drug resistance to examine the presence of R factors. They were highly resistant to one or more of six drugs including tetracycline (TC), chloramphenicol (CM), streptomycin (SM), sulfanilamide (SA), carbenicillin (CPC), and kanamycin (KM). Three FP
−
, auxotrophic mutants of
P. aeruginosa
were used as recipients, which had been made resistant to either rifampin (RMP) or KM by in vitro mutation. Each donor was mated with each of the three recipients, and 45 strains were found to transfer their resistance to one or more recipients. A second series of conjugation experiments using 45 exconjugants as donors showed that 23 could transfer their resistance. We conclude that these strains carry R factors that are transmissible to one or more recipients. Eleven carried resistance to (TC.CM.SM.SA.CPC), nine to (TC.CM.SM.SA), one to (TC.CM.SA.CPC), one to (TC.CM.SA), and one to (SM). All of these R factors could not be transmitted to other species belonging to the family
Enterobacteriaceae
.
Effect of Penicillin on the In Vivo Formation of the
d
-Alanyl-
l
-Alanine Peptide Cross-Linkage in Cell Walls of
Micrococcus luteus
Authors: Mirelman David , Bracha Rivka
Published: June 2012

Penicillin G was found to inhibit the formation of the
d
-alanyl-
l
-alanine cross-linkage in intact cells of
Micrococcus luteus
. This reaction was approximately 50-fold less susceptible to penicillin than the formation of the
d
-alanyl-
l
-lysine cross-linkage in the same organism. The presence of two penicillin-susceptible transpeptidation reactions that function in the incorporation of peptidoglycan precursors into the cell wall is proposed.
Purification and Characterization of Pertucin Produced by
Pseudomonas pertucinogena
Authors: Kawai Yoko
Published: June 2012

Pertucin, a bacteriocin active against phase I organisms of
Bordetella pertussis
, was extracted from
Pseudomonas pertucinogena
, strain 190 or 6627, by freezing and thawing of bacteria-free agar medium and was purified by ammonium sulfate fractionation, dialysis, zinc chloride precipitation, and polyacrylamide gel electrophoresis. The specific activity of purified pertucin was approximately 80 times that of the crude extract. The purified pertucin preparation was homogeneous on ultracentrifugal analysis and polyacrylamide gel electrophoresis, and was found to be composed of protein (80%) and carbohydrate (20%), the latter assumed not to be bound covalently to the protein. Neither nucleic acids nor lipids were demonstrated. N-terminal analysis by dansylation revealed only methionine in strain 190 and only glycine in strain 6627. The isoelectric point was found to be 4.8, and the molecular weight was estimated to be 31,500. Amino acid analysis of the protein moiety demonstrated that it contained all of the common amino acids with somewhat more of the hydrophilic amino acids. With respect to thermostability, pH stability, and effects of metal ions and various buffers, pertucin behaves like a protein and is stable in 0.05 M tris(hydroxymethyl)aminomethane buffer, pH 8.0, containing 0.01 M Ca
2+
.
Cinoxacin: Effectiveness Against Experimental Pyelonephritis in Rats
Authors: Holmes D. H. , Ensminger P. W. , Gordee R. S.
Published: June 2012

The antimicrobial activity of cinoxacin, 1-ethyl-4(1H)-oxo-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid, previously reported as compound 64716, was determined and compared with other antimicrobial agents at a dosage of 12 mg/kg once daily in a descending pyelonephritis rat model with
Escherichia coli
and
Proteus mirabilis
as infecting organisms. Cinoxacin was considerably more effective than either nalidixic acid or oxolinic acid when all three were administered orally at 3 mg/kg four times daily. The presence of demonstrable serum activity with a high recovery in urine indicates cinoxacin possesses highly desirable properties of an effective oral chemotherapeutic agent for urinary tract infections.
Comparison of Spectinomycin Hydrochloride and Aqueous Procaine Penicillin G in the Treatment of Uncomplicated Gonorrhea
Authors: Duanćić Ana , Fiumara Nicholas J. , Alpert Susan , Lee Yhu-Hsiung , Tarr Philip I. , Rosner Bernard , McCormack William M.
Published: June 2012

Men and women with uncomplicated gonorrhea were randomly assigned to receive aqueous procaine penicillin G (2,400,000 U for men; 2,400,000 U daily for 2 days for women) or spectinomycin hydrochloride (2.0 g for men; 4.0 g for women). Among men who returned for post-treatment evaluation within 10 days, treatment failures were noted among 16 (20.3%) of 79 men who received penicillin and 8 (9.5%) of 84 men who received spectinomycin (P < 0.1). Similarly, 6 (13.3%) of 45 women who received penicillin and 3 (6.5%) of 46 women who received spectinomycin had positive endocervical cultures for
Neisseria gonorrhoeae
at the time of the post-treatment examination (
P
= not significant).
Comparison of In Vitro Antibacterial Activities of Gentamicin and Verdamicin
Authors: Yu Pauline K. W. , Washington John A.
Published: June 2012

The in vitro activities of verdamicin and gentamicin were studied in parallel against 1,049 bacterial isolates. Verdamicin demonstrated activity similar to that of gentamicin against members of the family
Enterobacteriaceae
and against
Pseudomonas aeruginosa
at 2 and 8 μg/ml, respectively.
Proteus rettgeri
and
Providencia stuartii
were notably more susceptible to verdamicin. The new aminoglycoside was also highly active against staphylococci but was not effective against group D streptococci.
Comparison of a Radioimmunoassay with an Enzymatic Assay for Gentamicin
Authors: Minshew Barbara H. , Holmes Randall K. , Baxter Charles R.
Published: June 2012

A radioimmunoassay and an enzymatic assay for gentamicin have been compared. The correlation coefficient for results of gentamicin assays performed by the two methods with 45 serum specimens was 0.90. A similar standard curve for the radioimmunoassay was obtained with gentamicin complex, with gentamicin Cl, Cla, or C2, or with sisomicin as ligand, but tobramycin did not compete with [
3
H]gentamicin for binding to the antiserum.
Amikacin: a Rapid and Sensitive Radioimmunoassay
Authors: Lewis John E. , Nelson Jerald C. , Elder Harvey A.
Published: June 2012

A rapid, sensitive, and specific radioimmunoassay has been developed for the measurement of amikacin, a new semisynthetic aminoglycoside antibiotic. Antisera were produced by immunizing rabbits with amikacin conjugated to porcine thyroglobulin. Sera were screened for amikacin antibodies with
3
H-labeled amikacin. Free and bound radioactivity were separated by the second antibody method. As little as 5 ng of the antibiotic can be measured in serum, cerebrospinal fluid, and urine. The standard curve is unaffected by pH (5–11), ionic strength (0.01 M to 0.3 M), MgCl
2
or CaCl
2
(1 to 8 mM/liter), or urea (10–300 mg/100 ml). The antibodies raised to amikacin are not able to distinguish between kanamycin and amikacin. The cross reactivity of all other antibiotics tested was <0.1%. Co-incubation of first and second antibody allows for a 30-min incubation period, making the assay useful for
stat
determinations. The standard curve is linear on a logit-log plot, allowing for rapid computer analysis of the standard curve, interpolation of sample values, and quality-control monitoring.
Chloramphenicol Resistance in
Myxococcus xanthus
Authors: Burchard Robert P. , Parish J. H.
Published: June 2012

Derivatives of
Myxococcus xanthus
FB
t
resistant to chloramphenicol (25 μg/ml) arose spontaneously with a frequency of approximately 10
−7
. One of these organisms (FB
t
Cam
1
r
) was characterized. FB
t
Cam
1
r
showed a unique type of phenotypic instability. After transfer from medium containing chloramphenicol to medium lacking the drug, resistance was lost after approximately one generation. The loss resulted in a sharp drop in the total number of chloramphenicol-resistant organisms and was not due to segregation of chloramphenicol-susceptible organisms during growth. Cell-free extracts of strain FB
t
Cam
1
r
converted chloramphenicol to acetyl chloramphenicols in a fashion implicating activity of chloramphenicol acetyltransferase. This activity was lost simultaneously with the loss of chloramphenicol resistance after removal of the drug from cultures. Organisms with a similar phenotype to FB
t
Cam
1
r
could be produced at high frequencies when strain FB
t
was exposed to low concentrations of chloramphenicol (2 to 5 μg/ml), to 3-acetylchloramphenicol (25 μg/ml), or to 1,3-diacetylchloramphenicol (25 μg/ml). Since strain FB
t
is capable of deacetylating acetyl chloramphenicols, these effects are probably all due to low concentrations of chloramphenicol. In the presence of chloramphenicol, FB
t
Cam
1
r
produced fruiting bodies and myxospores on fruiting agar; however, glycerol-induced myxospore formation was inhibited. In the absence of the antibiotic, chloramphenicol resistance was maintained by glycerol-induced myxospores.
Phosphonoacetic Acid in the Treatment of Experimental Herpes Simplex Keratitis
Authors: Gerstein Douglas D. , Dawson Chandler R. , Oh Jang O.
Published: June 2012

In a rabbit model of herpes simplex corneal ulceration, 5% phosphonoacetic acid solution or ophthalmic ointment suppressed clinical disease and virus replication. The effect of 5% phosphonoacetic acid ointment was equivalent to that of 0.5% idoxuridine ointment in the treatment of this established herpetic eye infection.
Effect of Rifampin on Nasal Carriage of
Staphylococcus aureus
Authors: Sande Merle A. , Mandell Gerald L.
Published: June 2012

Initial studies indicate that rifampin may be useful for the treatment of
Staphylococcus aureus
infections. Because bacterial resistance to rifampin may develop rapidly, its widespread use could result in the emergence of a resistant flora. This study evaluates the effectiveness of rifampin in reducing the nasal carriage of
S. aureus
and the rate at which resistant mutants emerge in a tuberculosis hospital where the drug was widely used. Anterior nares cultures were performed four times over a 13-month period. Carriage rates of
S. aureus
were 1.7% in 227 patients receiving rifampin, 7.8% in 190 patients receiving other antituberculous therapy, and 14.2% in 98 hospital employees (rifampin-treated versus other patients,
P
< 0.003; rifampin-treated versus employees,
P
< 0.001; employees versus other patients,
P
= 0.157). All four strains of
S. aureus
isolated from patients on rifampin therapy were rifampin resistant. All 16 strains isolated from patients not on rifampin and 15 of 16 strains isolated from hospital personnel were susceptible. One instance of apparent spread of a rifampin-resistant organism occurred in a hospital attendant who had never received rifampin.
Effects of Dihydrostreptomycin on Ribosome Function In Vivo: Lack of Correlation Between Changes in Ribosome Patterns and Growth
Authors: Kogut Margot , Prizant Elaine
Published: June 2012

In vivo treatment of susceptible
Escherichia coli
cultures with low concentrations of dihydrostreptomycin leads to a decline in polysomes and a corresponding increase in 70
S
particles which behave as run-off ribosomes, as well as free 30
S
and 50
S
subunits. We have examined the timing and extent of these effects on ribosomes and compared them to the effects of this antibiotic on growth and protein synthesis. We have shown that no changes in ribosome distribution are observed until growth inhibition by dihydrostreptomycin is almost complete. Thus, intracellular dihydrostreptomycin can inhibit growth and net protein synthesis without apparently affecting the ribosome cycle. Since it is known that the antibiotic combines with free 30
S
subunits, the question is how such combination can bring about the observed inhibition of protein synthesis and growth. We suggest that specific interaction of intracellular antibiotic with proteins of the 30
S
subunits allows repeated use of the ribosome cycle by such affected particles, but with selective misreading of certain amino acid codons as terminator codons, so that they produce incomplete polypeptide chains. The cumulative effect of such a mechanism would lead to eventual cessation of protein synthesis and growth.
New Polyene Antifungal Antibiotic Produced by a Species of
Actinoplanes
Authors: Wagman G. H. , Testa R. T. , Patel M. , Marquez J. A. , Oden E. M. , Waitz J. A. , Weinstein M. J.
Published: June 2012

A new species of
Actinoplanes
, which has been deposited with the designation NRRL 5325 at the Northern Utilization Research and Development Division of the U. S. Department of Agriculture, produces a polyene antifungal complex designated as Sch 16656. The complex, consisting of one major and three minor components, is isolated from the fermentation broth by a solvent extraction procedure and purified by precipitation methods. The major component is a heptaene and is highly active in vitro and in vivo against
Candida albicans
. It is active also against strains of
Torulopsis
and is significantly more potent orally than candicidin in mice against
Candida
infections.
Double-Blind Comparison of Phlebitis Produced by Cefazolin Versus Cephalothin
Authors: Shemonsky Natalie K. , Carrizosa Jaime , Kaye Donald , Levison Matthew E.
Published: June 2012

In a double-blind study with each patient as his own control, 1 g of cefazolin and 2 g of cephalothin were administered intravenously every 6 h to 20 patients in opposite arms for a period of 48 h each. The degree of phlebitis was significantly more severe with cephalothin than with cefazolin (
P
< 0.05); however, neither the incidence of phlebitis nor the time of onset of phlebitis was significantly different between the two drugs.
Inhibition of Pathogenic Enteric Bacteria by Hyperbaric Oxygen: Enhanced Antibacterial Activity in the Absence of Carbon Dioxide
Authors: Bornside George H. , Pakman Leonard M. , Ordoñez Alfred A.
Published: June 2012

The antibacterial effects of 24-h exposures to high-pressure oxygen in relation to environmental CO
2
were studied at 3 atm absolute (ata) and at 1 ata. Eight gram-negative, aerobic and facultatively aerobic, pathogenic enteric bacteria (
Salmonella typhosa, Salmonella paratyphi, Salmonella schottmuelleri, Shigella dysenteriae, Shigella flexneri, Proteus vulgaris, Pseudomonas aeruginosa
, and
Escherichia coli
) were exposed as shallow-broth cultures and agar surface cultures. Although broths supplemented with 0.2% glucose permitted some growth of
Salmonella typhosa, Salmonella schottmuelleri, Shigella dysenteriae
, and
Shigella flexneri
during exposure to high-pressure oxygen in the presence of CO
2
, the other species grew only after the exposure, indicating a bacteriostatic effect. Both bacteriostatic and bactericidal effects were demonstrated on the surface of Trypticase soy agar, where killing of
Salmonellea typhosa, Proteus vulgaris
, and
Pseudomonas aeruginosa
was significantly greater after exposure to pure O
2
at 3 ata than at 1 ata. At 3 ata, significantly more killing occurred upon exposure of all species (except
Shigella dysenteriae
and
S. flexneri
) on an agar surface to 100% O
2
as compared with exposure to a mixture of 95% O
2
+ 5% CO
2
. Thus, deprivation of CO
2
during exposure to pure O
2
enhanced the bactericidal effect of high-pressure oxygen.
Economical Agar Dilution Technique for Susceptibility Testing of Anaerobes
Authors: Hauser K. J. , Johnston J. A. , Zabransky R. J.
Published: June 2012

A reliable agar dilution technique has been developed enabling the clinical laboratory to perform antibiotic susceptibility tests on significant anaerobes with ease and economy.
Structure-Activity of Sulfones and Sulfonamides on Dihydropteroate Synthetase from
Neisseria meningitidis
Authors: Ho Richard I. , Corman Leonard , Morse Stephen A. , Schneider Herman
Published: June 2012

The molecular interaction of various sulfones and sulfonamides with partially purified dihydropteroate synthetase from
Neisseria meningitidis
M-166 has been examined. The mode of action of the sulfones was similar to that of the sulfonamides. Both groups of drugs were competitive inhibitors of dihydropteroate synthetase with respect to
p
-aminobenzoate in a partially purified enzyme preparation. 4,4′-Diaminodiphenylsulfone was three times more effective than sulfadiazine and nine times more effective than sulfanilamide as a competitive inhibitor of dihydropteroate synthetase. The inhibitory activity of 4-amino-4′-acetamidodiphenylsulfone and 4-amino-4′-formamidodiphenylsulfone in this system eliminated their prior conversion to 4,4′-diaminodiphenylsulfone as a requirement for activity.
Some Effects of Subinhibitory Concentrations of Penicillin on the Structure and Division of Staphylococci
Authors: Lorian Victor
Published: June 2012

A strain of
Staphylococcus aureus
was planted on filter membranes placed on Trypticase soy agar (BBL). After incubation, the membranes with growing staphylococci were transferred to Trypticase soy agar containing a subinhibitory concentration of penicillin (one-third minimal inhibitory concentration) and again incubated. The membranes were then returned to drug-free agar and incubated once more. Counts of the colony-forming units and electron microscopy were carried out at several time intervals. When grown on agar containing penicillin, the staphylococci formed what appeared to be abnormally large cells with multiple and unusually thick septa. Examination of a number of sections showed that these large cells were in reality clusters of staphylococci that had divided but failed to separate. When these large cells were subsequently grown on drug-free agar, smaller cells and normal staphylococci emerged. Subinhibitory concentrations of penicillin do not kill staphylococci; they seem to inhibit lysis of cross walls, preventing the separation of otherwise divided cells.
Candihexin Polyene Macrolide Complex: Physicochemical Characterization and Antifungal Activities of the Single Components
Authors: Martin Juan F. , McDaniel Lloyd E.
Published: June 2012

The candihexin complex produced by a natural mutant of
Streptomyces viridoflavus
has been resolved into eight components. At least six of them, having hexaene chromophores, can be separated directly by thin-layer chromatography. The four major components, candihexins A, B, E, and F, account for about 90% of the total complex. They have been isolated and purified to homogeneity. All the major components were found to have macrolide lactone rings with all-
trans
hexaene chromophores. Candihexins A and B have compositions and molecular weights similar to candidin, the heptaene polyene macrolide produced by the parent
S. viridoflavus
, whereas candihexins E and F show smaller molecular weights and rather different elementary compositions. Candihexins A and B yield the amino sugar mycosamine upon hydrolysis, but no sugar was found in hydrolysates of candihexins E and F. Candihexins A and B have high antifungal activity against yeasts and filamentous fungi. The amino sugar-lacking candihexins E and F show no antifungal activity at levels of 100 μg/ml.
Mersalyl: a Diuretic with Antiviral Properties
Authors: Kramer M. J. , Cleeland R. , Grunberg E.
Published: June 2012

Mersalyl (Salyrgan), an organic mercurial diuretic, was tested against human and animal viruses with in vivo model infections in mice and tissue culture systems. Mersalyl was active against coxsackieviruses A21 and B1 in mice if administered intraperitoneally immediately after infection. No effect was observed if intraperitoneal treatment was delayed 1 or 2 h postinfection, or if treatment was administered either subcutaneously or per os. Topical treatment with a 5% aqueous solution of mersalyl produced a statistically significant effect against herpes simplex dermatitis in mice but the substance was inactive against systemic infections in mice with herpes simplex as well as Columbia SK, influenza, Semliki Forest, and Sendai viruses. Contact inactivation of coxsackieviruses A21 and B1 and herpes simplex virus was observed, but mersalyl was inactive in tissue culture against coxackieviruses A21 and B1, herpes simplex, influenza, rhinovirus, Semliki Forest, Sendai, and vaccinia viruses.
Inhibition of Experimental Deoxyribonucleic Acid Virus-Induced Encephalitis by 9-β-
d
-Arabinofuranosylhypoxanthine 5′-Monophosphate
Authors: Allen Lois B. , Thompson Jodia M. , Huffman John H. , Revankar Ganapathi R. , Tolman Richard L. , Simon Lionel N. , Robins Roland K. , Sidwell Robert W.
Published: June 2012

9-β-
d
-Arabinofuranosylhypoxanthine 5′-monophosphate (ara-HxMP) significantly controlled the development of encephalitis produced by deoxyribonucleic acid viruses in mice. In most experiments the activities of ara-HxMP and 9-β-
d
-arabinofuranosyladenine (ara-A) were determined simultaneously. In the intracerebral (target organ) and intravenous therapy experiments, ara-HxMP had a pronounced advantage over ara-A since the water solubility of ara-HxMP enabled it to be used in much higher concentrations. In experiments where the two drugs were administered intraperitoneally or orally they exhibited similar activity. In several intraperitoneal therapy experiments ara-HxMP was tested alone, using various treatment schedules and dosages. In these experiments, efficacy was observed in groups that had treatments initiated as late as 72 h after virus inoculation.
Evaluation of a Topical Interferon Inducer in Experimental Influenza Infection in Volunteers
Authors: Douglas R. Gordon , Betts Robert F. , Simons Ruth L. , Hogan Patricia W. , Roth Frieda K.
Published: June 2012

The prophylactic and/or therapeutic effect of a low-molecular-weight interferon inducer, CP-20,961, was tested in a double-blind placebo controlled study of experimental influenza A/England/42/72 (H
3
N
2
) infection in normal volunteers. Ten volunteers received CP-20,961 and 10 received placebo. Interferon was detected in nasal secretions of nine of the former and three of the latter group (P < 0.05). Seven in each group became ill, and severity of illness was not different. Also, quantitative virus shedding patterns and antibody response were not different between the two groups. The negative result may have been due to the relatively low quantities of interferon induced.