bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial Activity of Amine Oxides: Mode of Action and Structure-Activity Correlation
Authors: Šubík Július , Takácsová Gizela , Pšenák Mikuláš , Devínsky Ferdinand
Published: June 2012

The effect of
N
-alkyl derivatives of saturated heterocyclic amine oxides on the growth and metabolism of microorganisms has been studied. 4-Dodecylmorpholine-
N
-oxide inhibited the differentiation and growth of
Bacillus cereus
, of different species of filamentous fungi, and of the yeast
Saccharomyces cerevisiae
. For vegetative cells, the effect of 4-dodecylmorpholine-
N
-oxide was lethal. Cells of
S. cerevisiae
, after interaction with 4-dodecylmorpholine-
N
-oxide, released intracellular K
+
and were unable to oxidize or ferment glucose. The functions of isolated yeast mitochondria were also impaired. 4-Dodecylmorpholine-
N
-oxide at growth-inhibiting concentrations induced rapid lysis of osmotically stabilized yeast protoplasts, with the rate of lysis a function of temperature and of amine oxide concentration. A study of the relationships between structure, antimicrobial activity, and cytolytic activity was made with a group of structurally different amine oxides involving a series of homologous 4-alkylmorpholine-
N
-oxides, 1-alkylpiperidine-
N
-oxides, 1-dodecylpyrrolidine-
N
-oxide, 1-dodecylperhydroasepine-
N
-oxide, and
N,N
-dimethyldodecylamine oxide. Disorganization of the membrane structure after interaction of cells with the tested amine oxides was primarily responsible for the antimicrobial activity of the amine oxides. This activity was found to be dependent on the chain length of the hydrophobic alkyl group and was only moderately influenced by other substituents of the polarized
N
-oxide group.
Physiological Effects of an Antimycotic Azasterol on Cultures of
Saccharomyces cerevisiae
Authors: Hays P. R. , Neal W. D. , Parks L. W.
Published: June 2012

The yeast
Saccharomyces cerevisiae
has been studied during cultivation with a naturally occurring antimycotic azasterol. At very low concentrations (1.0 to 10.0 ng/ml), where growth retardation is not observed, an unusual sterol, ergosta-8,14-dien-3β-ol, accumulates in high concentrations. Upon removal of the azasterol from the culture, the 8,14-diene is converted to ergosterol. Much smaller amounts of another 8,14-sterol, but with an additional unsaturation, have also been observed. Total sterol accumulation is higher in cultures containing subinhibitory levels of the antimycotic agent than the amounts of normal sterol accumulation in control cultures. With between 10 and 100 ng of azasterol per ml a transitory cessation of growth is observed from which the culture is able to recover. At much higher concentrations growth inhibition and even cell lysis results. Competitive inhibition of sterol 24(28)methylene reductase is demonstrated.
Transfer of Plasmid-Borne Beta-Lactamase in
Neisseria gonorrhoeae
Authors: Baron Ellen S. , Saz Arthur K. , Kopecko Dennis J. , Wohlhieter John A.
Published: June 2012

Neisseria gonorrhoeae
strain GC82 contains a plasmid specifying a β-lactamase (β-Lam
+
). Mixed incubation of strain GC82 with a penicillin-susceptible (β-Lam
−
), streptomycin-resistant mutant of strain GC9 results in the expression of β-lactamase activity and streptomycin resistance in the transcipients. The frequency of transfer of the plasmid-specified resistance to penicillin seems to be proportional to the initial input ratio of the mating mixture of donor to recipient and to correlate positively with bacterial density. Cell-to-cell transmission of the deoxyribonucleic acid (DNA) appears to be by a conjugal mechanism or, alternatively, by an as yet undescribed transducing phage. Additionally, whole-cell DNA from a β-lactamase-producing strain could be used to transform streptomycin-resistant recipients, resulting in the expression of both β-lactamase activity and streptomycin resistance in the transformants, and purified gonococcal plasmid DNA transformed
Escherichia coli
but not the gonococcus. Circular DNA extracted from donor GC82 comprised three molecular species (approximately 2.7, 4.8, and 25 megadaltons [Mdal]), whereas the recipients GC9-S (Str
r
) contained only the 2.7-Mdal cryptic DNA species. DNA from the GC9-S82 (Str
r
, β-Lam
+
) transcipient contained a 4.8-Mdal species in addition to the cryptic molecular species (2.7 Mdal). The finding that the transcipient will not retransfer β-lactamase is consistent with the hypothesis that the 25-Mdal plasmid promotes mobilization of the smaller 4.8-Mdal R plasmid.
Temperature Effects on Minimum Inhibitory and Bactericidal Concentrations of Cell Wall Antibiotics in
Streptococcus faecalis
Authors: Hinks Eileen T. , Daneo-Moore Lolita , Braverman Shirley
Published: June 2012

The minimal inhibitory and bactericidal concentrations were determined at 30 and 37°C for several antibiotics affecting cell wall biosynthesis. The test organism,
Streptococcus faecalis
ATCC 9790, possesses a single autolytic enzyme and does not produce penicillinase. Penicillin, methicillin, and, possibly, bacitracin appeared more effective at 37 than at 30°C. Vancomycin, ristocetin, and phosphonomycin appeared equally effective at both temperatures, and cycloserine appeared consistently more active at 30 than at 37°C.
In Vitro Activity of Rosamicin Against
Neisseria
and
Haemophilus
, Including Penicillinase-Producing Strains
Authors: Sanders Christine C. , Sanders W. Eugene
Published: June 2012

Rosamicin was significantly more active against
Haemophilus
and
Neisseria
than are many antibiotics currently used to treat or prevent infection caused by these organisms. This enhanced activity was also observed against penicillinase-producing strains.
Comparison of the Effects of Two Lipophilic Acids, Hexachlorophene and Decanoate, on
Bacillus subtilis
Authors: Levin Barbara Chernov , Freese Ernst
Published: June 2012

The minimal growth-inhibitory amount of either hexachlorophene (HCP) or decanoate stopped growth, respiration, adenosine 5′-triphosphate synthesis, and amino acid transport of
Bacillus subtilis
in a culture containing amino acids and citrate as carbon sources. The electron transport system was not affected by this dose. Addition of 27.8 mM glucose or 10 mM malate to an inhibited culture did not reverse the binding of HCP or decanoate to the cells, but it allowed resumption of growth, respiration, and adenosine 5′-triphosphate synthesis, as the glucose or malate then supplied the needed carbon. The addition of glucose or malate did not reverse amino acid transport inhibition caused by decanoate, but it did reverse that due to HCP. However, if the dose of HCP was raised in the presence of glucose or malate, only growth and amino acid transport were affected; this indicates that both HCP and decanoate act at their minimal growth inhibitory doses by inhibiting substrate transport. As active transport of amino acids and ketoacids depends on the proton gradient and the membrane potential of the cells, we conclude that the primary effect of these lipophilic acids is the destruction of the proton-motive force.
Acriflavine-Resistant Mutant of
Streptococcus cremoris
Authors: Sinha R.P.
Published: June 2012

Selection for resistance to acriflavine in
Streptococcus cremoris
resulted in cross-resistance to the drugs neomycin, streptomycin, ethidium bromide, mitomycin C, and proflavine. Furthermore, the mutants showed resistance to lytic bacteriophages to which the parental strain was sensitive, and, unlike the parent, the mutants grew well at higher temperatures (40°C). Revertants selected independently either for temperature sensitivity or for acriflavine sensitivity lost resistance to all the drugs and dyes but retained the bacteriophage resistance phenotype. The acriflavine-resistant mutation resulted in an increase in resistance by the bacterial cells to sodium dodecyl sulfate, a potent solvent of lipopolysaccharide and lipoprotein. It is suggested that the acriflavine resistance mutation determines the synthesis of a membrane substance resistant to higher temperatures.
Nonconjugative Plasmids Encoding Sulfanilamide Resistance
Authors: Mitsuhashi Susumu , Inoue Kunio , Inoue Matsuhisa
Published: June 2012

Nonconjugative plasmids encoding sulfanilamide (Sa) resistance were demonstrated at a high frequency in
Shigella
and
Escherichia coli
strains resistant to sulfanilamide. These Sa plasmids were all compatible with the standard plasmids used in compatibility testing. The sizes of seven Sa plasmids were measured by electron microscopy and ranged from 1.79 to 2.08 μm, corresponding to 3.5 to 3.9 megadaltons.
In Vitro Activity of Cefaclor, a New Orally Administered Cephalosporin Antibiotic
Authors: Santoro Jerome , Levison Matthew E.
Published: June 2012

The in vitro antibacterial activity of cefaclor, cephalothin, and cephalexin against 261 clinical isolates of
Staphylococcus aureus
and
Enterobacteriaceae
was compared. Cefaclor and cephalexin were about equally active against
S. aureus
. Cefaclor was the most active cephalosporin against
Escherichia coli, Proteus mirabilis
, and
Klebsiella pneumoniae
. The effect on the antimicrobial activity using a relatively high and low inoculum was pronounced for cefaclor when compared with that of cephalothin.
Comparison of the Nephrotoxicity of Netilmicin and Gentamicin in Rats
Authors: Bowman Ralph L. , Silverblatt Fredrick J. , Kaloyanides George J.
Published: June 2012

The nephrotoxicity of netilmicin relative to that of gentamicin was examined in Sprague-Dawley rats. Balance studies were performed on rats injected with netilmicin or gentamicin (50 mg/kg per day for 14 days, 100 mg/kg per day for 8 days, and 150 mg/kg per day for 8 days). Control rats were injected with saline. Both drugs caused a dose-related decrease in urine osmolality and increases in urine volume, water intake, and serum creatinine; however, the magnitude of these changes was significantly less in netilmicin- than in gentamicin-injected rats. Light microscopy of renal tissue revealed less proximal tubular cell necrosis in netilmicin- than in gentamicin-injected rats. There was no significant difference between the renal cortical concentrations of the two drugs. Both drugs stimulated uptake of
p
-aminohippurate in rat renal cortical slices to the same degree. The data indicate that netilmicin is less nephrotoxic than gentamicin in rats, that the difference in nephrotoxicity cannot be explained by a difference in drug concentration in the renal cortex, and that the ability of aminoglycosides to stimulate the organic acid transport system of proximal tubular cells does not correlate with their nephrotoxic potential.
Factors Involved in Beta-Lactam Antibiotic Resistance in
Pseudomonas aeruginosa
Authors: Ohmori Hitoshi , Azuma Akiko , Suzuki Yoji , Hashimoto Yoshinobu
Published: June 2012

A temperature-sensitive mutant, strain SS, which is assumed to be devoid of β-lactamase activity and deficient in a permeability barrier to antibiotics, was isolated from a β-lactamase-less mutant, strain L-2, derived from
Pseudomonas aeruginosa
IFO 3080. By comparing the β-lactam antibiotic susceptibility between strains IFO 3080, L-2, and SS, the involvement of both β-lactamase and a permeability barrier in determining the β-lactam antibiotic resistance was estimated.
Antiviral Activity of Ribavirin in Rotavirus Gastroenteritis of Mice
Authors: Schoub Barry D. , Prozesky O. W.
Published: June 2012

Ribavirin was inactive against the rotavirus of murine gastroenteritis; this may be due to the presence of guanosine inhibitors in the gut.
Unusual Effects of Penicillin G and Chloramphenicol on the Growth of
Moraxella osloensis
Authors: DeLeys Robert J. , Juni Elliot
Published: June 2012

Growth of exponential-phase liquid cultures of
Moraxella osloensis
was inhibited by 0.5 U of penicillin G per ml. For this organism, low concentrations of penicillin acted primarily in a bacteriostatic rather than in a bactericidal manner. At higher concentrations of penicillin some killing did take place, but the rate of killing was rather slow and appeared to be independent of penicillin concentration. Microscopic observation of cells from penicillin-treated cultures showed little or no cellular swelling or lysis. The total cell count did not decrease significantly during 6 h of incubation in 5,000 U of penicillin per ml. The rates of respiration, nucleic acid synthesis, and protein synthesis were not affected by the presence of penicillin. Attempts to counteract the bactericidal action of high concentrations of penicillin with growth inhibitory concentrations of chloramphenicol were unsuccessful, since chloramphenicol itself was more bactericidal than penicillin for
M. osloensis
.
In Vitro Activities of Five Oral Cephalosporins Against Aerobic Pathogenic Bacteria
Authors: Shadomy Smith , Wagner Gerald , Carver Melinda
Published: June 2012

Cefaclor (Lilly 99638) and cefatrizine (BL-S640, SK&F 70771) are orally absorbed, broad-spectrum semisynthetic cephalosporins. They were compared in vitro with cephalexin, cephaloglycin, and cepharadine against a variety of aerobic pathogenic bacteria by an agar dilution procedure. Cefaclor and cefatrizine were found to be similar or superior to cephalexin, cephaloglycin, and cephradine in terms of activity against gram-positive cocci other than enterococci. Only cefatrizine demonstrated any potentially useful activity against some susceptible isolates of enterococci. Cefaclor and cefatrizine also were highly active, equally or more so than the other oral cephalosporins, against several gram-negative species including
Escherichia coli, Enterobacter aerogenes
, and
Klebsiella pneumoniae
. None of the cephalosporins were particularly active against
Enterobacter cloacae
. Both cefaclor and cefatrizine were active against
Proteus mirabilis
; cefatrizine was uniquely active against indolepositive
Proteus
species.
Emergence in a Burn Center of Populations of Bacteria Resistant to Gentamicin, Tobramycin, and Amikacin: Evidence for the Need for Changes in Zone Diameter Interpretative Standards
Authors: Minshew Barbara H. , Pollock Helen M. , Schoenknecht Fritz D. , Sherris John C.
Published: June 2012

From July 1974 through June 1976, a number of isolates of
Escherichia coli, Klebsiella pneumoniae
, and
Pseudomonas aeruginosa
from the Burn Center exhibited a shift to smaller zone diameters with gentamicin than did isolates from the general hospital population. Although many had zone diameters ≥13 mm and would have been considered susceptible by this breakpoint, they were found to have minimal inhibitory concentrations (MICs) of ≥8 μg of gentamicin per ml by agar dilution testing. Zone diameters and MICs of gentamicin, tobramycin, and amikacin were subsequently compared for 168 isolates from both the Burn Center and general hospital. The results revealed many isolates that fell into presently used gentamicin- and tobramycin-“susceptible” categories by disk diffusion tests but were resistant by MIC. The data indicated that criteria for gentamicin disk diffusion testing should include an intermediate or indeterminate category, and that the limits of the intermediate category for tobramycin and amikacin should be expanded.
Radiometric Determination of the Concentration of Amphotericin B in Body Fluids
Authors: Hopfer Roy L. , Gröschel Dieter
Published: June 2012

A new assay was developed to determine the concentration of amphotericin B in body fluids. The Bactec radiometric system was used to measure CO
2
production by a test strain,
Candida albicans
MDA 448, in the presence of amphotericin B. After 5-h incubation, drug concentrations as low as 0.2 μg/ml could be detected. The results are comparable to those of the commonly used agar diffusion assay with
Paecilomyces varioti
.
Consequence of Cerulenin-Released Beta-Lactamase in Clinical Coliforms
Authors: Choudhury Tapan K. Kar
Published: June 2012

Periplasmic β-lactamase of certain clinical coliforms was released, without affecting cell viability, by perturbation of the outer membrane utilizing the fatty acid-mimicking antibiotic cerulenin. Release of such compartmentalized β-lactamase, at high population density, seems to provide an extra margin of resistance to the organisms against cephaloridine.
Simplified Radioenzymatic Assay for Chloramphenicol
Authors: Robison Leon R. , Seligsohn Robert , Lerner Stephen A.
Published: June 2012

A simplified radioenzymatic assay for chloramphenicol was developed by eliminating the need for cumbersome extraction procedures. After the acetylation of chloramphenicol with [
14
C]acetyl coenzyme A in the presence of chloramphenicol acetyltransferase, the reaction mixture was added to a toluene-based scintillation fluid. Since
14
C-acetylated chloramphenicol is more soluble than [
14
C]acetyl coenzyme A in toluene, the radioactive product could be counted directly. The rapidity of this assay, as well as its accuracy, precision, and specificity, makes it particularly suitable for clinical use. In contrast to previous reports of enzymatic assays for chloramphenicol, we have found that results of the assay of standards prepared in serum were up to 25% higher than those of standards prepared in saline, cerebrospinal fluid, or urine.
Frequency of Resistance to Kanamycin, Tobramycin, Netilmicin, and Amikacin in Gentamicin-Resistant Gram-Negative Bacteria
Authors: Seligman Stephen J.
Published: June 2012

In vitro evaluation of 66 epidemiologically distinct, gentamicin-resistant, gram-negative isolates from four hospitals revealed that 92% were kanamycin resistant, 44% were netilmicin resistant, 41% were tobramycin resistant, and 6% were amikacin resistant. Combined resistance to gentamicin, tobramycin, and netilmicin occurred in 30% of the strains. Although the resistance percentage to amikacin was the lowest of the three newer agents, two strains were resistant to all of the aminoglycosides tested.
Antiviral Effects of Amphotericin B Methyl Ester
Authors: Jordan George W. , Seet Elizabeth C.
Published: June 2012

The methyl ester of amphotericin B (AME) is water soluble, retains antifungal activity, and is significantly less toxic in mammals than amphotericin B. In contrast to amphotericin B, which is not water soluble, AME exhibits antiviral effects against vesicular stomatitis virus, herpes simplex virus types 1 and 2, Sindbis virus, and vaccinia virus in a plaque reduction assay. No antiviral effects could be demonstrated against the unenveloped adenovirus type 4 or echovirus type 11. The extent of virus inactivation was found to be dependent upon the AME concentration, contact time, and temperature. No consistent effect of the virus concentration on the probability of plaque-forming unit inactivation could be determined. The antiviral effects of AME were partially antagonized by the presence of serum. Binding of AME to vesicular stomatitis virus was demonstrated by the comigration of drug and virus in linear sucrose gradients. AME represents a new class of antiviral agents with activity at concentrations relevant to therapeutics. Sterol components of the host cell membrane that become incorporated into the viral envelope are postulated as the site of reaction with AME.
Characterization of Cell Wall Polymers Secreted into the Growth Medium of Lysis-Defective Pneumococci During Treatment with Penicillin and Other Inhibitors of Cell Wall Synthesis
Authors: Hakenbeck Regine , Waks Susan , Tomasz Alexander
Published: June 2012

Autolysin-defective pneumococci secrete large quantities of choline-containing cell wall polymers into the growth medium during treatment with inhibitors of peptidoglycan synthesis. The secreted polymers were separated into three fractions by a combination of gel filtration on agarose and sodium dodecyl sulfate-gel electrophoresis. Fraction I had a high apparent molecular size and contained the Forssman antigen in complex with material exhibiting properties of cell wall teichoic acid. Choline-containing polymers of as yet uncharacterized structure were present in both fractions IIA and IIB, and fraction IIA also contained peptidoglycan components.
Purification and properties of beta-lactamase from Bacteroides fragilis
Authors: Britz M L , Wilkinson R G
Published: June 2012

Beta-Lactamase activity was detected either biologically or using the chromogenic cephalosporin 87/312 in 20 clinical isolates of Bacteroides fragilis with penicillin G minimal inhibitory concentrations of 10 to 100 micrograms/ml. Strain AM78 (minimal inhibitory concentration, greater than 1,000 micrograms/ml) was used to optimize the conditions for production, assay, and storage of the enzyme. The enzymes are cell associated, with less than 1% of activity being found in culture fluids during growth, and can be released from the cell surface by modified osmotic shock procedure. This procedure causes concomitant release of cyclic phosphodiesterase activity. Substrate profiles and the effects of inhibitors were determined for enzymes partially purified by osmotic shock release and gel filtration. The enzymes are cephalosporinases with some penicillinase activity and are inhibited by p-chloromercuribenzoate, cloxacillin, and carbenicillin. The molecular weight, as determined by gel filtration, is 29,000 to 31,000. A method for the purification of the beta-lactamase from strain AM78 is described: the specific activity of the purified enzyme was 3,424 U/mg, about 3,000-fold that of the crude, cell-associated enzyme.
In vitro study of clavulanic acid in combination with penicillin, amoxycillin, and carbenicillin
Authors: Wise R , Andrews J M , Bedford K A
Published: June 2012

The activity of clavulanic acid alone and in combination with penicillin, amoxycillin, and carbenicillin was studied. Marked reductions in the minimum inhibitory concentrations (MICs) for a wide spectrum of beta-lactamase-producing clinical isolates were found. Of particular interest were the decreased MICs of penicillin for Bacteroides fragilis and beta-lactamase-producing strains of Neisseria gonorrhoea in the presence of the clavulanic acid. Beta-lactamase-producing strains of Escherichia coli, Klebsiella spp., and indole-negative Proteus also showed considerably increased susceptibility to amoxycillin in combination with clavulanic acid. Two beta-lactamase-producing strains of Pseudomonas aeruginosa remained resistant to carbenicillin in the presence of clavulanic acid.
Treatment of osteomyelitis and septic arthritis with cefazolin
Authors: Fass R J
Published: June 2012

Sixteen cases of severe osteomyelitis and septic arthritis caused by staphylococci, streptococci, gonococci, and a variety of gram-negative bacilli were treated with 4 to 8 g of parenteral cefazolin per day; nine received subsequent therapy with oral cephalexin or ampicillin. Of 16 infections, 15 were apparently cured. Cefazolin concentrations in those patients were: serum (peak), 25 to 216 micrograms/ml; synovial fluid, 24 to 46 micrograms/ml; and bone, 3.2 to 10.6 micrograms/g. Bacterial pathogens had minimal inhibitory concentrations of cefazolin of 2 micrograms or less per ml and seemed to be eradicated from foci of infection during therapy. One infection in a diabetic patient did not respond; despite high concentrations of cefazolin in serum, no detectable antibiotic was present in her infected metatarsal, and the infecting Escherichia coli (minimal inhibitory concentration, 16 micrograms/ml) was not eradicated during therapy. Concentrations of cefazolin in bone in 10 uninfected patients who received 1-g intramuscular doses prophylactically before surgery were also measured. Concentrations in bones from those who had normal renal function ranged from less than 0.6 to 2.8 micrograms/g.
Influence of R-plasmid RP1 of Pseudomonas aeruginosa on cell wall composition, drug resistance, and sensitivity to cold shock
Authors: Kenward M A , Brown M R , Hesslewood S R , Dillon C
Published: June 2012

R-plasmid RP1 was transferred to Pseudomonas aeruginosa cells, as indicated by their resistance to carbenicillin, ampicillin, cephaloridine, kanamycin, and tetracycline, and by the presence of a periplasmic beta-lactamase. The wild-type cells (RP1-) were lysed by ethylenediaminetetraacetic acid but not by ethylene-glycol-bis(2-aminoethyl ether)-N,N-tetraacetic acid, whereas cells carrying the plasmid (RP1+) were resistant to both these chelating agents. RP1+ and RP1- strains were both sensitive to the lytic action of polymyxin B and the lethal action of cold shock, but the effect was less marked in the RP1+ cultures. A proportion of the RP1+ cells surviving cold shock lost resistance to carbenicillin, tetracycline, and kanamycin. The chemical composition of whole cells and cell walls of RP1+ differed from that RP1- in the content of cation, phospholipid, and markers for lipopolysaccharide and peptidoglycan. Differences in cell wall composition, response to ethylenediaminetetraacetic acid and polymyxin B, and the effects of cold shock are all compatible with the hypothesis that RP1 confers changes in the cell envelope, probably in the outer membrane, of P. aeruginosa.
Interactions between Neisseria sicca and viridin B, a bacteriocin produced by Streptococcus mitis
Authors: Law D J , Dajani A S
Published: June 2012

Viridin B, a bacteriocin produced by Streptococcus mitis (mitior), is bactericidal to Neisseria sicca. Oxygen consumption by actively growing N. sicca cultures ceased immediately upon exposure to viridin B. Adenosine triphosphate production was slightly enhanced within 1 h of exposure to the bacteriocin but was subsequently repressed. The uptake and incorporation of glucose was prevented in the presence of viridin B. The bacteriocin also blocked uptake of an amino acid mixture in chloramphenicol-pretreated cells. Pretreatment or concomitant treatment with a variety of antibiotics known to inhibit specific synthetic pathways did not alter the inhibition of macromolecular synthesis produced by the bacteriocin. Although viridin B blocks protein and nucleic acid syntheses, no degradation of such macromolecules was observed. The inhibitory effects of viridin B on macromolecular synthesis and on viability required the presence of sufficient nutrients to allow active metabolism of N. sicca. The bacteriocin did not inhibit viability or macromolecular synthesis in anaerobically incubated N. sicca. Thus, active, oxidative metabolism by N. sicca cells is essential for viridin B action. A model for viridin B action is proposed.
Mode of action of the Haemophilus bactericidal factor
Authors: Streker R G , Venezia R A , Robertson R G
Published: June 2012

Haemocin, a bacteriocin produced by Haemophilus influenzae b, caused pronounced cell elongation of the sensitive strains H. influenzae Rd and Escherichia coli CR34 thyA. In the sensitive strains, haemocin markedly inhibited the synthesis of deoxyribonucleic acid (DNA) but did not affect either ribonucleic acid or protein synthesis. The observed inhibition in synthesis of DNA was not due to degradation of preexisting DNA. The data suggest that haemocin may specifically inhibit DNA synthesis.
Comparative in vitro activities of SCE-129, sulbenicillin, gentamicin, and dibekacin against Pseudomonas
Authors: Tsuchiya K , Kondo M
Published: June 2012

Against sulbenicillin- and gentamicin-susceptible strains of Pseudomonas aeruginosa, SCE-129 was about 10 times more active than sulbenicillin and had a similar activity to gentamicin and dibekacin. Sulbenicillin-resistant strains of P. aeruginosa were moderately resistant to SCE-129, whether these strains were gentamicin-resistant or not. Gentamicin-resistant strains of P. aeruginosa were resistant to dibekacin but not to SCE-129. Against P. maltophilia, the minimum inhibitory concentration of SCE-129 resembled those of sulbenicillin, gentamicin, and dibekacin. Most strains of P. cepacia were moderately resistant to SCE-129 and sulbenicillin and highly resistant to gentamicin and dibekacin.
5,6-Dihydro-5-Azathymidine: In Vitro Antiviral Properties Against Human Herpesviruses
Authors: Renis Harold E.
Published: June 2012

5,6-Dihydro-5-azathymidine (DHAdT), a novel water-soluble nucleoside antibiotic, inhibits herpes simplex virus type 1 (HSV-1) in appropriately infected cell cultures to a greater extent than herpes simplex virus type 2 (HSV-2). Vaccinia virus was less susceptible than HSV-2, and pseudorabies virus yields were not reduced at the concentrations studied. Plaque formation by varicella-zoster virus was suppressed by DHAdT. DHAdT was slightly toxic to cells at concentrations that were inhibitory for HSV-1 and varicella-zoster virus. Thymidine and deoxyuridine completely reversed the anti-HSV-1 activity of DHAdT, whereas deoxycytidine was partially effective. Compared with other nucleoside analogs with activity for HSV-1, DHAdT was less active than 5-iodo-2′-deoxyuridine or 1-β-
d
-arabinofuranosylcytosine and nearly equipotent with 9-β-
d
-arabinofuranosyladenine.
Irreversible Effects of Serum Proteins on Beta-Lactam Antibiotics
Authors: O'Callaghan Cynthia H.
Published: June 2012

The chromogenic cephalosporin nitrocefin (87/312) demonstrates rapid and visible instability to serum from many species. This phenomenon was distinct from serum binding, being significantly slower. Destruction of another cephalosporin, 10485, by serum appeared to account for some anomalous results during investigation into its human pharmacokinetics. Many cephalosporins of very different structures also showed serum instability, unrelated to their degrees of serum binding as measured by plate assay. Extrapolation could not be made from one species to another with regard to either binding or instability. Small changes in the chemical structures of the 3- and 7-substituents of the cephalosporins made profound changes in their susceptibility to serum attack. The decomposition is pH dependent, occurring more slowly at acid pH, and is due to a high-molecular-weight component of serum that resists boiling for several minutes. Isoelectric focusing of serum from several animal species gave various species-specific bands that decomposed nitrocefin. The inactivation of nitrocefin was not entirely parallel with that of 10485 and was inhibited by it. All other β-lactam compounds tested also inhibited the reaction, much greater concentrations usually being necessary when the inhibitor was stable to serum. The complex that causes breakdown of the β-lactam compounds is not necessarily the same as the one causing serum binding. It is postulated that serum may affect most other β-lactam antibiotics in a similar way, although in most cases, this only occurs to a very slight extent.
Medium-Dependent Variation in Bactericidal Activity of Antibiotics Against Susceptible
Staphylococcus aureus
Authors: Peterson Lance R. , Gerding Dale N. , Hall Wendell H. , Schierl Elizabeth A.
Published: June 2012

Staphylococcus aureus
resistant to bactericidal activity of antibiotics caused sepsis in three patients. Bacteriological and clinical responses were not achieved until serum and tissue fluid levels of administered antibiotics exceeded the minimum bactericidal concentration (MBC) of the infecting organism. Fifteen clinical isolates of
S. aureus
were tested in brain heart infusion broth and Mueller-Hinton broth for the MBC of gentamicin, vancomycin, clindamycin, oxacillin, cefazolin, and cephalothin. Results showed significant eightfold or greater broth-dependent differences in the MBC of at least one antibiotic against 87% (13/15) of strains tested. The MBC was unpredictable and varied with the strain, antibiotic, and medium used. No controlled studies are available to indicate the clinical significance of the MBC demonstrated in different media. The necessity for treating serious infection with bactericidal drugs has not yet been established; however, in septicemia such as that caused by bacterial endocarditis, bacteriostatic antibiotics have generally failed to eradicate the infection, whereas bactericidal agents have often been curative. Therefore, in patients unresponsive to usual antistaphylococcal therapy, we suggest that MBC testing be performed in at least two media and that treatment be instituted with antibiotics demonstrating the lowest MBC in all media used.
New Plasmid (pTU512), Mediating Resistance to Penicillin, Erythromycin, and Kanamycin, from Clinical Isolates of
Staphylococcus aureus
Authors: Kono Megumi , Sasatsu Masanori , Ubukata Kimiko , Konno Masatoshi , Fujii Rhochi
Published: June 2012

Multiply drug-resistant strains of
Staphylococcus aureus
were isolated from pediatric patients with severe staphylococcal infections in 1974 through 1976. Resistance to benzylpenicillin, erythromycin, and kanamycin was jointly eliminated without exception from these multiply drug-resistant strains by treatment with ethidium bromide. It was also found that the triple drug resistance in a representative strain, TK512-200, was always transduced to a susceptible strain simultaneously. Moreover, a single class of plasmid deoxyribonucleic acid was isolated from a transductant and found to be 14.4 ± 0.6 μm in length, with a molecular weight corresponding to 29.8 × 10
6
. From these results, it is concluded that the plasmid (pTU512) is a new one, mediating resistance to penicillin, erythromycin, and kanamycin.
In Vitro Activity of Rifampin Alone and in Combination with Nafcillin and Vancomycin Against Pathogenic Strains of
Staphylococcus aureus
Authors: Tuazon Carmelita U. , Lin Melody Y. C. , Sheagren John N.
Published: June 2012

Twenty strains of
Staphylococcus aureus
isolated from patients with endocarditis were examined in vitro for susceptibility to rifampin, nafcillin, and vancomycin and to combinations of rifampin with nafcillin or vancomycin. Minimum bactericidal concentrations of rifampin ranged from 0.0031 to 0.0125 μg/ml, of nafcillin ranged from 0.078 to 0.312 μg/ml, and of vancomycin ranged from 0.312 to 1.25 μg/ml. The combination of rifampin with nafcillin was synergistic for 12 strains; the combination of rifampin plus vancomycin was synergistic for 5 of the isolates.
Mechanism of Penicillin-Erythromycin Synergy on Antibiotic-Resistant
Staphylococcus aureus
Authors: Allen Norris E. , Epp Janet K.
Published: June 2012

Clinically isolated strains of
Staphylococcus aureus
that are inducibly resistant to both erythromycin and penicillin were susceptible to a combination of the two antibiotics. The synergistic effect of the combination results from an inhibition of penicillinase induction by erythromycin, sparing penicillin and allowing this drug to inhibit growth. When resistance to erythromycin is constitutive rather than inducible, the combination is no longer synergistic.
Comparative Susceptibility of Four Kinds of Pathogenic Fungi to Amphotericin B and Amphotericin B Methyl Ester
Authors: Huston Alice C. , Hoeprich Paul D.
Published: June 2012

The activity of amphotericin B methyl ester was compared with that of amphotericin B, using
Candida albicans
(34 isolates),
Torulopsis glabrata
(12 isolates),
Filobasidiella neoformans
(stat. conid.
Cryptococcus neoformans
) (14 isolates), and
Coccidioides immitis
(37 isolates) and tube dilution in a totally synthetic, completely defined medium (SAAMF) with inocula of 10
4
colony-forming units per ml. Minimal inhibitory concentrations were read after 24 h at 34°C for
C. albicans
and
T. glabrata
, and after 48 h at 34°C for
C. immitis
and
F. neoformans
. Minimal lethal concentrations were determined by subculture of 10% of the volume of the cultures without evident growth onto Sabouraud glucose agar medium. Overall, amphotericin B methyl ester was slightly less active than amphotericin B, with the differences attaining statistical significance for: (i) inhibition of
C. albicans
and
T. glabrata
and (ii) killing of
T. glabrata
.
Dissociation Between Ion Permeability and the Lethal Action of Polyene Antibiotics on
Candida albicans
Authors: Chen Winston C. , Chou Dong-Lang , Feingold David S.
Published: June 2012

Kinetic data on potassium release from and killing of
Candida albicans
by the four polyene antibiotics amphotericin B, amphotericin B methyl ester hydrochloride, nystatin, and nystatin methyl ester hydrochloride are presented. The nystatins were relatively more effective than the amphotericins in causing potassium release rather than killing. These data suggest that the aqueous channels or pores formed by the polyene antibiotics are not central to the lethal action of the drugs.
In Vitro Studies of Piperacillin, a New Semisynthetic Penicillin
Authors: Winston Drew J. , Wang Daisy , Young Lowell S. , Martin William J. , Hewitt William L.
Published: June 2012

Piperacillin, a new semisynthetic penicillin, was compared with other semisynthetic penicillins, cephalosporins, and aminoglycosides by the agar dilution method against 3,600 isolates of facultative gram-negative bacilli,
Bacteroides fragilis
, and enterococci. At 64 μg/ml, piperacillin inhibited 90% of the isolates in each group of organisms tested except for
Escherichia coli
(83% inhibited by 64 μg/ml). Compared with carbenicillin, piperacillin had a 16-fold increase in activity by weight against
Pseudomonas aeruginosa
and the enterococcus, an 8-fold increase against
Serratia marcescens
, and a 4-fold increase against
B. fragilis
and
Enterobacter
species. Piperacillin was highly active against carbenicillin-resistant
Klebsiella pneumoniae
and inhibited many aminoglycoside-resistant organisms. Except for
P. aeruginosa
, the minimum bactericidal concentration of piperacillin was usually within one tube dilution of the minimum inhibitory concentration. Approximately one-third of the gram-negative bacilli were inhibited synergistically by piperacillin plus amikacin, but no synergy could be demonstrated against enterococci. Piperacillin's in vitro activity against gram-negative bacilli was similar to gentamicin's except that it also included
B. fragilis
, and piperacillin was decidedly superior to presently available penicillins against
K. pneumoniae
.
Effect of Triethylenetetramine Dihydrochloride on the Antibiotic Susceptibility of
Pseudomonas aeruginosa
Authors: Light B. , Riggs H. G.
Published: June 2012

A chelating agent, triethylenetetramine dihydrochloride, interacted synergistically in vitro with both gentamicin and carbenicillin against a clinical isolate of
Pseudomonas aeruginosa
designated Ps 15. The minimal inhibitory concentrations of carbenicillin and gentamicin for Ps 15 in a 50% serum-Trypticase soy broth were 250 and 72.9 μg/ml, respectively. However, addition of triethylenetetramine dihydrochloride to the 50% serum-Trypticase soy broth reduced the minimal inhibitory concentration of both antibiotics approximately 10-fold. A comparison of the growth of Ps 15 in 50% serum-Trypticase soy broth containing either of the antibiotics showed that a rapid decrease in the percentage of survivors only occurred when the chelating agent was present.
In Vitro Antibacterial Activity of Amikacin and Ticarcillin, Alone and in Combination, Against
Pseudomonas aeruginosa
Authors: Yoshikawa Thomas T. , Shibata Sharon A.
Published: June 2012

In vitro antimicrobial susceptibility studies using amikacin and ticarcillin, alone and in combination, were performed on 20 strains of
Pseudomonas aeruginosa
. All strains were susceptible to amikacin, and ticarcillin was active against 16 of the 20 strains. Enhanced anti-pseudomonas activity could be demonstrated with the combination of amikacin and ticarcillin.
Metabolic Fate of SCE-129, a New Antipseudomonal Cephalosporin, After Parenteral Administration in Rats and Dogs
Authors: Tanayama Shigeharu , Yoshida Kiyoshi , Kanai Yoshio
Published: June 2012

Disposition of [
14
C]SCE-129 was studied in rats and dogs after intramuscular (i.m.) or intravenous (i.v.) injection. In rats, the plasma level of i.m. [
14
C]SCE-129 attained a peak at 15 min after dosing and then declined with a half-life of 35 min, whereas the half-life after an i.v. dose was 26 min. The area under the plasma level curve within 2 h after the i.m. dose was 85% of that after the i.v. dose. Intramuscular injection of [
14
C]SCE-129 into dogs gave a peak plasma level at 30 min and a half-life of 60 min. In both rats and dogs, the plasma levels of
14
C were closely similar to those of the unchanged antibiotic, which was weakly bound to plasma protein. The rat tissue level of i.m. [
14
C]SCE-129 was maximum at 15 min, with the highest concentration in the kidney, followed by plasma, adrenal, lung, heart, thymus, gastrointestinal wall, and liver, and the lowest in the brain. The antibiotic barely entered erythrocytes of rats and dogs. Whole-body autora-diographic studies showed that i.m. [
14
C]SCE-129 scarcely crossed the rat placenta.
14
C was detected in the milk of rats given i.m. [
14
C]SCE-129. In both rats and dogs, almost all of the dosed
14
C was excreted in urine within 24 h as the unaltered antibiotic, with only small amounts appearing in feces via bile. Thus, these findings evidenced a rapid absorption and wide distribution of i.m. SCE-129, followed by extensive renal elimination as the unaltered antibiotic.
Method for Qualitative Determination of 2-Deoxystreptamine
Authors: Lee B. K. , Condon R. G. , Patel M. , Oden E. M. , Waitz J. A.
Published: June 2012

We have developed a qualitative method to assay for the presence of 2-deoxystreptamine in hydrolysates of crude aminoglycoside preparations using a 2-deoxystreptamine-requiring idiotrophic mutant. The assay involves (i) incubation of a 2-deoxystreptamine-requiring mutant with 1 mg of a hydrolyzed preparation from a crude unknown antibiotic mixture per ml, and (ii) examination of the resultant incubation mixture for production of antibiotic(s) by disk assay.
Detection of Antibiotic-Producing
Streptomyces
Inhabiting Forest Soils
Authors: Nkanga Enefiok-J- , Hagedorn Charles
Published: June 2012

A modified agar overlay technique was developed for detecting antibiotic production by
Streptomyces
isolates and compared with two routinely used overlay procedures and the shake flask-disk assay method. Two types of inhibitory patterns could be discerned in the modified overlay method, and one of these was always exhibited by
Streptomyces
isolates which produced extractable antimicrobial substances. In a preliminary screening of 600 isolates, higher numbers of antibiotic-producing streptomyces were detected with the modified overlay procedure than with the streak or pour overlay method and the shake flask assay. The modified overlay distinguished between antibiotic production and other antagonistic effects. The inhibitory agents extracted after 6 days of culture growth on the modified overlay agar were of a higher concentration and more stable over longer periods of time than those recovered from shake flasks. It was observed that acidoduric streptomyces produced a greater proportion of antibiotics against gram-negative bacteria than did neutrophilic cultures, and this effect was greatest with the isolates from the most acidic soils. The neutrophiles were more active against gram-positive bacteria and, upon antibiotic classification, it appeared that the neutrophilic and acidoduric cultures from various soils produced different antimicrobial compounds.
Mechanism of the Antimicrobial Action of Pyrithione: Effects on Membrane Transport, ATP Levels, and Protein Synthesis
Authors: Chandler Carol J. , Segel Irwin H.
Published: June 2012

Pyrithione is a general inhibitor of membrane transport processes in fungi. A brief preincubation of
Penicillium
mycelia with pyrithione resulted in a marked decrease in the activities of a variety of independently regulated transport systems, including those for inorganic sulfate, inorganic phosphate, methylamine (actually, the NH
4
+
permease), choline-
O
-sulfate, glucose,
l
-methionine (a specific system), and several hydrophobic
l
-α-amino acids (the general amino acid permease). The degree of inhibition at any fixed pyrithione concentration and exposure time increased as the pH of the incubation medium was decreased. This result strongly suggests that the active species is the un-ionized molecule and that pyrithione acts by collapsing a transmembrane ΔpH driving force. The degree of transport inhibition caused by a given concentration of pyrithione increased with increasing time of exposure to the inhibitor. However, exposure time and pyrithione concentration were not reciprocally related. At “low” pyrithione concentrations, transport inhibition plateaued at some finite value. This observation suggests that the fungi can detoxify low levels of the inhibitor. The concentration of pyrithione required for a given degree of growth inhibition increased as the experimental mycelial density increased. This phenomenon was consistent with the suggestion that the fungi are capable of inactivating pyrithione.
In Vivo Studies with Ambruticin in Murine Histoplasmosis
Authors: Shadomy Smith , Utz Christopher J. , White Stanley
Published: June 2012

Ambruticin (W7783) was evaluated in vivo in mice subacutely or nonlethally infected with
Histoplasma capsulatum
. Results were compared with those obtained with amphotericin B, the drug of choice in human histoplasmosis. In one experiment, ambruticin was shown to be capable of curing infected animals as evidenced by totally negative liver and spleen cultures obtained when mice were sacrificed after 4 weeks of oral treatment with 150 mg of drug per kg per day. The 50% cure dose for ambruticin was between 75 and 150 mg/kg per day; the 50% cure dose for oral amphotericin B in this experiment was between 1.56 and 6.25 mg/kg per day. In a second experiment, both oral ambruticin (150 mg/kg per day) and oral amphotericin B (25 mg/kg per day) were again curative, but to a lesser degree than in the first experiment. Biological cures were obtained with both drugs after 3 and 4 weeks of treatment but not after 2 weeks.
Carbon Catabolite Regulation of Cephalosporin Production in
Streptomyces clavuligerus
Authors: Aharonowitz Yair , Demain Arnold L.
Published: June 2012

Cephalosporin production by
Streptomyces clavuligerus
is regulated by some type of carbon catabolite control. Increasing concentrations of preferred carbon sources, such as glycerol and maltose, decreased production of the antibiotics. Poorer carbon sources, such as α-ketoglutarate and succinate, led to high specific production of cephalosporins and shifted the dynamics of fermentation to a greater degree of association with growth. The results support the concept that the phase in which a product is made by a microorganism is not a function of the particular molecule produced, but rather of the nutritional environment presented to the organism.
In Vitro Susceptibility of
Mycoplasma hyopneumoniae
and
Mycoplasma hyorhinis
to Fifty-One Antimicrobial Agents
Authors: Williams Phletus P.
Published: June 2012

By a tube dilution assay technique, 51 antimicrobial agents were singly tested against 9 strains of
Mycoplasma hyopneumoniae
and 1 strain of
M. hyorhinis
for the purpose of obtaining information useful for selecting an agent for testing in vivo against porcine mycoplasmal pneumonia. Based on determining minimal inhibitory concentrations and chemically grouping the agents into nine classes, all
M. hyopneumoniae
strains were found resistant to penicillins and peptides and susceptible to sulfonamides and tetracyclines, and, in other classes, were either susceptible or resistant depending on the particular agent being tested. Strains were susceptible to the same 33 of the 51 agents. Minimal inhibitory concentrations ranged from 0.06 to 9.20 μg/ml.
M. hyorhinis
was susceptible to 19 of the 33 agents that
M. hyopneumoniae
was susceptible to. Minimal inhibitory concentrations ranged from 0.03 to 8.10 μg/ml. All strains of
M. hyopneumoniae
differed from
M. hyorhinis
in that they were susceptible to cephaloglycin and nitrofurazone.