bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial Action of Esters of Polyhydric Alcohols
Authors: Conley Anthony J. , Kabara Jon J.
Published: June 2012

A broth dilution method was used to determine the minimal inhibitory concentration of a series of fatty acid esters of polyhydric alcohols against gram-negative and gram-positive organisms. Gram-negative organisms were not affected. Gram-positive organisms were inhibited as follows. Of the monoglycerol esters, monoglycerol laurate was the most active. Esters of polyglycerols (tri-, hexa-, and decaglycerol esters) were generally active when the fatty acid had chain lengths of 8 to 12 carbon atoms. Sucrose esters, when active, except for laurate, are more active than the free fatty acid. The spectrum of antimicrobial action of esters of polyhydric alcohols is narrower when compared with the free acids.
Microbial Kinetics and Dependencies of Individual and Combined Antibiotic Inhibitors of Protein Biosynthesis
Authors: Garrett Edward R. , Heman-Ackah Samuel M.
Published: June 2012

The generation rate constants for the steady-state growth of antibiotic-inhibited
Escherichia coli
have the same formal dependency on concentration for deoxylincomycin, lincomycin (phase I), erythromycin, clindamycin, and U24729A. They may be kinetically classified as a group A, in which the first three compounds comprise a subgroup A
1
and the latter two a subgroup A
2
. Generation rate constants initially decrease linearly with concentration but asymptotically approach zero at higher concentrations. With tetracycline or chloramphenicol, the generation rate decreases linearly with all concentrations, and these compounds may be kinetically classified as group B. Combining an antibiotic from group A with one from group B gives a response equal to that obtained with equivalent amounts of each antibiotic alone, and there are no significant effects from the order of antibiotic addition. However, combinations of an A
1
with an A
2
antibiotic are antagonistic, and there are significant effects from the order of addition. The dependencies of generation rate constants in the presence of these antibiotics can be rationalized by a receptor site model that considers varying degrees of the rate of drug transfer and drug inactivation in the organism.
Antiviral Effect of 3,4-Dihydro-1-Isoquinolineacetamide Hydrochloride in Experimental Human Rhinovirus Infection
Authors: Togo Yasushi , Schwartz Andrew R. , Hornick Richard B.
Published: June 2012

Double-blind trials were conducted in volunteers to evaluate the efficacy of the prophylactic 3,4-dihydro-1-isoquinolineacetamide hydrochloride (DIQA) treatment against rhinovirus type 24 challenge. Ten men received a 7-day course of DIQA treatment and 11 men received a placebo. The intranasal viral challenge dose was 10 mean tissue culture infective doses. The oral administration of 1 g prechallenge and 2 g a day for 6 consecutive postchallenge days did not prevent the development of colds. Nine drug-treated men and 10 controls developed rhinovirus illness. However, the illnesses of the drug-treated men were mild. Rhinorrhea occurred less frequently and was more mild in the drug-treated group. The challenge virus was recovered from 80% of these subjects in both groups, but almost twice the number of challenge viruses were isolated from the controls than from the drug-treated men. The prophylactic DIQA therapy appears to suppress the cold syndrome and to reduce virus excretion, although its effect is marginal. Additional clinical trials are warranted to confirm the antirhinoviral effect of this drug.
Expression of R Factor-Mediated Resistance to Tetracycline in
Escherichia coli
Minicells
Authors: Franklin T. J. , Foster S. J.
Published: June 2012

The induction and expression of tetracycline resistance in R
+
minicells from
Escherichia coli
is incomplete, suggesting that some chromosomally mediated function is necessary for the full expression of tetracycline resistance.
Efficacy of Trimethoprim and Sulfamethoxazole in the Prevention and Treatment of
Pneumocystis carinii
Pneumonitis
Authors: Hughes Walter T. , McNabb Paul C. , Makres Thomas D. , Feldman Sandor
Published: June 2012

A combination of trimethoprim and sulfamethoxazole was effective in the prevention and treatment of
Pneumocystis carinii
pneumonitis in cortisonetreated rats. Although all of 15 untreated rats died with
P. carinii
pneumonitis, none of 15 given trimethoprim-sulfamethoxazole prophylactically acquired the infection. After
P. carinii
pneumonitis was established, 9 of 14 rats recovered after treatment with trimethoprim-sulfamethoxazole compared with only 2 of 14 treated with pentamidine isethionate. Rifampin and clindamycin, separately or in combination with pentamidine, were ineffective in the prevention and treatment of
P. carinii
infection.
Thermal Inactivation as a Means of Inhibiting the Serum-Associated Deamination of 9-β-
d
-Arabinofuranosyladenine in Tissue Culture Media
Authors: Schwartz Pauline M. , Shipman Charles , Carlson Roger H. , Drach John C.
Published: June 2012

9-β-
d
-Arabinofuranosyladenine (ara-A) was deaminated to 9-β-
d
-arabinofuranosylhypoxanthine by adenosine deaminase present in fetal bovine serum, newborn calf serum, and calf serum used to supplement tissue culture media. Heating newborn calf serum or calf serum for 12 h at 56 C completely eliminated the enzymatic deamination of ara-A. The deaminase activity associated with fetal bovine serum was more refractory to heating, requiring 24 h for complete inactivation. The nutritive value of heat-inactivated calf serum did not differ significantly from that of unheated serum based on considerations of population doubling times, deoxyribonucleic acid synthesis, and relative cloning efficiencies of KB cells.
Rifampin: Inhibition of Ribonucleic Acid Synthesis After Potentiation by Amphotericin B in
Saccharomyces cerevisiae
Authors: Battaner E. , Kumar B. Vijaya
Published: June 2012

The inhibition of
Saccharomyces cerevisiae
growth by amphotericin B and rifampin was studied. Rifampin alone had no effect on growth or macromolecular syntheses. Lethal amounts of amphotericin B produced a late inhibition of ribonucleic acid (RNA) synthesis simultaneous with the arrest of growth and protein synthesis. In contrast, low doses of amphotericin B along with rifampin caused an early arrest of RNA synthesis, followed by a later arrest of growth and protein synthesis. Used with rifampin, amphotericin B thus appears to increase cell permeability for rifampin, which in turn inhibits RNA synthesis; such results are consistent with some reports of inhibition of yeast RNA polymerase function by rifampin. Experiments with petite mutants ruled out any special effect of the antibiotics on mitochondrial RNA synthesis, so that nuclear RNA synthesis is affected. Acrylamide gel analyses of RNA pulse-labeled after addition of the two antibiotics in synergy showed that synthesis of all major classes of RNA was progressively and uniformly inhibited.
Pharmacology of Amikacin in Humans
Authors: Bodey Gerald P. , Valdivieso Manuel , Feld Ronald , Rodriguez Victorio
Published: June 2012

Amikacin is a new aminoglycoside antibiotic which is active in vitro against most isolates of gram-negative bacilli. A dose of 300 mg/m
2
intramuscularly produced a highest mean serum concentration of 25.4 μg/ml with a mean serum concentration of 3.1 μg/ml at 8 h. The same dose intravenously produced a highest mean serum concentration of 52.4 μg/ml with a mean serum concentration of 2.1 μg/ml at 8 h. The mean urinary excretion during the first 6 h was 75 and 66%, respectively. When amikacin was administered at a dose of 150 mg/m
2
every 6 h, there was evidence of some drug accumulation. A loading dose of 150 mg/m
2
administered intravenously over 30 min followed by 200 mg/m
2
administered as a continuous infusion every 6 h maintained serum concentrations of 8 μg/ml. No major toxicity was observed with any of these drug regimens.
In Vitro Development of Resistance to Erythromycin, Other Macrolide Antibiotics, and Lincomycin in
Mycoplasma pneumoniae
Authors: Niitu Yasutaka , Hasegawa Sumio , Kubota Hideo
Published: June 2012

Mycoplasma pneumoniae
was made highly resistant to erythromycin in vitro by serial subculture in broth media containing erythromycin. The resistance developed to erythromycin was 200 μg/ml with the Mac strain, a prototype of
M. pneumoniae
, and 10 μg/ml with the Fukumura strain, an isolate. The erythromycin resistance was accompanied by cross resistance to other macrolide antibiotics (leucomycin, josamycin, spiramycin, and oleandomycin) and to lincomycin, but there was no resistance to vernamycin B. Resistance to the antibiotics developed in vitro or in vivo was stable after the microorganisms were repeatedly transferred in antibiotic-free media.
Mechanism of Silver Sulfadiazine Action on Burn Wound Infections
Authors: Fox Charles L. , Modak Shanta M.
Published: June 2012

The role of silver and sulfadiazine in the mechanism of action of silver sulfadiazine on burn wound infections was investigated. Silver, but not sulfadiazine, was bound by bacteria. Sulfadiazine did not act as an antibacterial agent in low concentrations, but exhibited specific synergism in combination with subinhibitory levels of silver sulfadiazine. The efficacy of silver sulfadiazine is thought to result from its slow and steady reactions with serum and other sodium chloride-containing body fluids, which permits the slow and sustained delivery of silver ions into the wound environs. In this circumstance, a relatively minute amount of sulfadiazine appears active.
Chromatography of Penicillins, Penicilloates, and Penicilloylamides on Dextran Gels
Authors: Hyslop Newton E. , Milligan Richard J.
Published: June 2012

The factors influencing the chromatographic behavior on dextran gels of penicillins and their derivatives were investigated by comparing elution profiles and partition coefficients (

K
D

and

K
AV

) of penicillins differing in side-chain structure and among penicillin derivatives of identical side-chain but different nuclear structure. Under the conditions of pH and ionic strength employed (pH 7.4, 0.145 M NaCl, 0.05 M PO
4
), side-chain adsorptive effects best explained the anomalous behavior of benzylpenicillin and of oxacillin and its chlorine-substituted analogues. Polar side-chain substituents, such as the amino group of ampicillin and the carboxyl group of carbenicillin, and cleavage of the β-lactam ring, exemplified by penicilloates and penicilloylamines, both appeared to interfere with side-chain-directed adsorption. The differential adsorption of penicillins and their derivatives to dextran gels is not only of theoretical interest relative to the mechanism of chromatography but of practical application to analytical and preparative procedures in penicillin chemistry.
Variables Influencing the In Vitro Susceptibilities of Herpes Simplex Viruses to Antiviral Drugs
Authors: Marks Melvin I.
Published: June 2012

Some of the variables in a microtiter tissue culture method for estimating antiviral susceptibility of herpes simplex viruses (HSV) were studied. Six antiviral drugs (5-iodo-2′-deoxyuridine, cytosine arabinoside, 9-β-arabinofuranosyladenine, isoprinosine, virazole, and 2-deoxy-
d
-glucose) and three tissue culture cell lines (primary rabbit kidney, WI-38, and rat brain) were studied. Four different inocula (10, 100, 1,000, and 2,000 mean tissue culture doses) and nine isolates of HSV were tested. Minimal inhibitory concentration was defined as a complete inhibition of cytopathogenic effect in tissue culture cells after 72 h of incubation. There was a direct relationship between the viral inocula and the minimal inhibitory concentration. There were also differences between the three tissue culture cell lines and among the different strains of herpesvirus. This was not type specific, and the strain differences were not consistent in different tissue culture lines. Cytosine arabinoside appeared to be the most active drug in vitro, with 5-iodo-2′-deoxyuridine intermediate in activity between cytosine arabinoside and 9-β-arabinofuranosyladenine; no significant cytotoxicity was encountered with these drugs. Isoprinosine, virazole, and 2-deoxy-
d
-glucose were not effective against any of the nine strains of HSV tested in this in vitro system; a comparison with previous studies indicates that their activity may be cell dependent. These results emphasize the importance of careful evaluation of in vitro test methods for the susceptibility testing of antiviral agents against HSV. Marked variability between strains and in vitro test systems caution against the application of these methods to in vivo situations until further studies are carried out.
Pleiotropic Antibiotic Resistance Mutations Associated with Ribosomes and Ribosomal Subunits in
Mycobacterium smegmatis
Authors: Yamada Takeshi , Masuda Kunitsugu , Shoji Ko , Hori Mitsuo
Published: June 2012

Viomycin-resistant strains isolated from
Mycobacterium smegmatis
demonstrated pleiotropic resistance to tuberactinomycin-
N
, capreomycin, streptomycin, and kanamycin as a result of mutational alteration of ribosomes, even though they were selected for resistance to a single antibiotic. The pleiotropic drug resistance of three mutants isolated by stepwise selection for resistance to viomycin was due to alteration of the 30
S
ribosomal subunit. One mutant, strain A, isolated independently by multiple-step selection to viomycin resistance, was resistant to viomycin, tuberactinomycin-
N
, and capreomycin through an alteration of the 50
S
ribosomal subunit, whereas it was sensitive to kanamycin but resistant to streptomycin through an alteration of the 30
S
ribosomal subunit. Three streptomycin-resistant strains, which were isolated by one-step selection at a high concentration of streptomycin, did not show significant co-resistance to any other antibiotics tested in culture and cell-free systems; streptomycin resistance in these mutants was localized on the 30
S
ribosomal subunit.
Cefamandole, a Cephalosporin Antibiotic with an Unusually Wide Spectrum of Activity
Authors: Neu Harold C.
Published: June 2012

The in vitro activity of cefamandole, 7-
d
-mandelamido-3-(1 methyl-1H-tetrazol-5 yethiomethyl)-3-cephem-4 carboxylic acid, was investigated. The majority of streptococci and pneumococci were inhibited by 0.1 μg/ml. Activity against
Staphylococcus aureus
was below that of cephalothin, but most strains were inhibited by 0.4 μg/ml. Enterococci were not inhibited by less than 25 μg/ml. Cefamandole was very active against most members of the
Enterobacteriaceae
, with 70% of
Escherichia coli
, 86% of
Klebsiella pneumoniae
, and 88% of
Proteus mirabilis
inhibited by 1.6 μg/ml. A number of
Enterobacter aerogenes, Proteus vulgaris
, and
Serratia marcescens
strains were inhibited by less than 25 μg/ml.
Pseudomonas
species were resistant. Cefamandole was more active than cephalothin, cephaloridine, or cephalexin against members of the
Enterobacteriaceae
. Inoculum size and type of medium had variable effects on the minimal inhibitory concentration, depending upon the particular strain tested. Strains of
Enterobacter, Serratia
, indole-positive
Proteus
species showed the greatest inoculum effect. Similarly, these species showed a several-fold difference of bactericidal and inhibitory levels. Resistance of cefamandole to hydrolysis by gram-negative beta-lactamase played a partial role in its activity, but some strains that hydrolyzed the agent were susceptible.
Susceptibility of Clinical Isolates of Bacteria to Cefoxitin and Cephalothin
Authors: Moellering Robert C. , Dray Marie , Kunz Lawrence J.
Published: June 2012

The susceptibility of 4,929 unselected clinical isolates of bacteria to cefoxitin and cephalothin was determined by the single-disk method, using a computer-associated electronic zone analyzer to obtain, record, and process measurements of sizes of zones of inhibition. Both cefoxitin and cephalothin were effective against most gram-positive strains, including
Staphylococcus aureus, S. epidermidis
, micrococci, and all streptococci except enterococci. The three strains of
Listeria monocytogenes
tested were susceptible to cephalothin but resistant to cefoxitin. There was little difference between the cefoxitin and cephalothin susceptibility of
Salmonellae, Citrobacter
sp.,
Enterobacter
sp.,
Proteus mirabilis
, and
Pseudomonas
sp. Cefoxitin was more effective then cephalothin against
Escherichia coli, Klebsiella
sp.,
Serratia
sp., indole-positive
Proteus
sp.,
Providence
sp.,
Flavobacter
sp.,
Herellea vaginicola
, and
Mima polymorpha
. Cefoxitin also appeared to exhibit enhanced activity, as compared with cephalothin, against
Bacteroides
sp. Thus cefoxitin appears to have a very broad antibacterial spectrum which is greater than that of cephalothin, especially against gram-negative strains.
Variation in Performance of the Serum Bactericidal Test
Authors: Pien F. D. , Vosti K. L.
Published: June 2012

Questionnaires were sent to 37 diagnostic microbiology laboratories to assess their methods for performance of the serum bactericidal test. Of the 28 responding laboratories, 26 utilized the test, with considerable variation among methods. Culture and dilution media included Trypticase soy, Mueller-Hinton, brain heart infusion, Columbia broth, dextrose phosphate, and pooled human serum. Several different schemes for dilution of the test serum were employed, including both micro and macro methods. The greatest variation occurred in the size of the bacterial inoculum, with only eight laboratories having a method for standardization of the inoculum. Other differences included the time of incubation, the method of subculture, and determination of the bactericidal end point. These studies emphasize the need for assessment of the variables in the performance of this test and for the development of a standard method for diagnostic laboratories.
Binding of [
14
C]Erythromycin to
Escherichia coli
Ribosomes
Authors: Pestka Sidney
Published: June 2012

Erythromycin binding to
Escherichia coli
ribosomes required K
+
and Mg
2+
. Under optimal conditions, the dissociation constant for erythromycin binding to
E. coli
ribosomes was found to be 1.0 × 10
−8
M and 1.4 × 10
−8
M at 24 C and 5 C, respectively. One molecule of [
14
C]erythromycin was bound to each 70
S
ribosome at equilibrium. Binding of erythromycin to ribosomes was rapid and reversible. The specific rate constants for the forward and reverse reactions were 1.7 × 10
7
liters per mol per min and 0.15 per min, respectively.
Post-Exposure Prophylaxis of Murine Rabies with Polyinosinic-Polycytidylic Acid and Chlorite-Oxidized Amylose
Authors: Harmon Maurice W. , Janis Burton , Levy Hilton B.
Published: June 2012

Chlorite-oxidized amylose (COAM), polyinosinic-polycytidylic acid [poly(I:C)], and combinations of the two drugs were evaluated for their interferon-inducing properties and their ability to protect mice against rabies infection. Post-exposure administration of one or two doses (100 μg each) of poly(I:C) significantly protected mice against rabies infection. Pretreatment of mice with COAM 3 h before poly(I:C) stimulation resulted in an enhancement of the interferon response. However, the increased interferon titers were not reflected by increased protection against rabies infection over that achieved with poly(I:C) therapy alone. Therapy with COAM alone did not protect mice against rabies but, rather, was associated with enhanced mortality.
Antivirion Effects of Streptovaricin Complex Against Friend Virus
Authors: Horoszewicz Julius S. , Leong Susan S. , Byrd Daniel M. , Carter William A.
Published: June 2012

The in vitro antivirion activities of five different streptovaricin complex lots against the polycythemic strain of the Friend virus were evaluated. The assay system was based on the inhibition of the Friend virus-induced spleen foci. The virus inactivation process was shown to be susceptible to variation in temperature, pH, and time. The antivirion activity and the acute toxicity for mice, as well as the optical properties of these streptovaricin complexes, do not co-vary; this suggests that their biological activities are not associated with a single molecular structure. In addition, the antivirion activity of the five preparations of streptovaricin complex differs about 30-fold, indicating that this activity does not reside in a major component of the complex.
Effect of Leucomycins and Analogues on Binding [
14
C]Erythromycin to
Escherichia coli
Ribosomes
Authors: Pestka Sidney , Nakagawa Akira , Ōmura Satoshi
Published: June 2012

We examined the effect of leucomycins, leucomycin derivatives, and other 16-membered macrolides (tylosin, niddamycin, spiramycin I, and spiramycin III) on [
14
C]erythromycin binding to ribosomes. Results of these studies enabled determination of the association and dissociation constants for the binding of each of these compounds to
Escherichia coli
ribosomes. In addition, the binding of the leucomycins and the leucomycin derivatives to ribosomes in general correlated with their antimicrobial activity.
Penicillin-Resistant Mechanisms in
Pseudomonas aeruginosa
: Effects of Penicillin G and Carbenicillin on Transpeptidase and
d
-Alanine Carboxypeptidase Activities
Authors: Suginaka Hidekazu , Ichikawa Akira , Kotani Shozo
Published: June 2012

A membrane fraction from
Pseudomonas aeruginosa
KM 338 was shown to catalyze in vitro peptidoglycan synthesis from uridine 5′-diphosphate-
N
-acetylmuramyl-
l
-alanyl-
d
- glutamyl-meso-diaminopimelyl-
d
-alanyl-
d
-alanine and uridine 5′-diphosphate-
N
-acetylglucosamine. Synthesized peptidoglycan was partially cross-linked by transpeptidation, which was accompanied by the release of
d
-alanine. This reaction was strongly inhibited by 25 and 50 μg of penicillin G and carbenicillin per ml respectively, whereas the intact cells were relatively resistant to penicillins (minimal inhibitory concentration of penicillin G and carbenicillin, 30 and 0.125 mg/ml, respectively). Soluble
d
-alanine carboxypeptidase present in
P. aeruginosa
KM 338 was studied as well, which was found almost completely inhibited by penicillin G and carbenicillin (10 μg/ml).
3-N Enzymatic Acetylation of Gentamicin, Tobramycin, and Kanamycin by
Escherichia coli
Carrying an R Factor
Authors: Le Goffic François , Martel Annie , Witchitz Janine
Published: June 2012

A new R factor-mediated gentamicin acetyltransferase obtained from a clinical isolate of gentamicin-, tobramycin-, and kanamycin-resistant
Klebsiella
was characterized. R factor R 176 was transferred to
Escherichia coli
K-12 LA 290 from a
Klebsiella
. Resistance transfer, minimal inhibitory concentrations of various aminoglycoside antibiotics, enzymatic inactivation, and the isoelectric point of the enzyme obtained were determined. We found that R factor R 176 could govern the enzymatic 3-N acetylation of gentamicin, tobramycin, and kanamycin, and isoelectric point determinations suggested that the enzymes governed by R 176 and R 135 are different. The genes responsible for resistance to gentamicin, tobramycin, and kanamycin govern the synthesis of an isoenzyme of AAC(3)I, which we propose to call AAC(3)II.
Antimicrobial Actions of Hexachlorophene: Inhibition of Respiration in
Bacillus megaterium
Authors: Frederick John J. , Corner Thomas R. , Gerhardt Philipp
Published: June 2012

Hexachlorophene (HCP) inhibits both endogenous and exogenous respiration (oxygen uptake) in
Bacillus megaterium
, without sparing by any of several substrates. The inhibition is maximal when the cells are treated with 8 μg of HCP per mg of cells (dry weight), which corresponds to the minimal lethal dose. Levels as low as 2 μg/mg are inhibitory but not lethal. HCP also inhibits the respiration of isolated
B. megaterium
membranes and can act on several components of the electron transport chain in the membranes and on soluble enzymes. Although both forms of nicotinamide adenine dinucleotide, reduced form dehydrogenase and malic dehydrogenase are inhibited by HCP, they are less susceptible than is oxygen uptake. The site of maximal sensitivity is nearer the terminal electron acceptor, but the exact location depends on the cytochrome composition of the membranes. If cytochromes b
1
, a, and a
3
are present, but not o, HCP inhibits electron transport on the substrate side of cytochrome b
1
; if cytochromes b
1
, a
3
, and o are present, but not a, the inhibition occurs on the oxygen side of cytochrome b
1
. Exogenous menadione, an analogue of menaquinone, reverses the inhibition in both circumstances. The primary lethal action of HCP thus appears to be respiratory inhibition at a site within the membrane-bound part of the electron transport chain.
Endogenous, Spontaneous Formation of Beta-Lactamase in
Staphylococcus aureus
Authors: Sachithanandam S. , Lowery D. L. , Saz A. K.
Published: June 2012

In a β-lactamase-inducible strain of
Staphylococcus aureus
, the enzyme appears spontaneously in the absence of added inducer during lag and early log phases of growth and then declines rapidly to low levels. The endogenous inducer responsible for appearance of the enzyme has been isolated and purified and characterized as a peptidoglycan, containing muramic acid, glucosamine, glutamic acid, alanine, lysine, and glycine. The inducing compound could be isolated from the cells only during the lag and early log phases and from no other later periods. The data obtained are consistent with the thesis advanced earlier from this laboratory that β-lactamase serves a cellular function in the producing cell more important and beyond its capability of hydrolyzing certain penicillins to the antibiotically inactive penicilloic acids.
Properties of an R Plasmid in
Pseudomonas aeruginosa
Producing Amikacin (BB-K8), Butirosin, Kanamycin, Tobramycin, and Sisomicin Resistance
Authors: Jacoby George A.
Published: June 2012

Pseudomonas aeruginosa
strain GN315, producing kanamycin acetyltransferase, can transmit a plasmid determining resistance to kanamycin, amikacin (BB-K8), butirosin, tobramycin, and sisomicin, but not gentamicin, to other pseudomonas strains. This plasmid, pMG5, belongs to the same incompatibility group as plasmids determining gentamicin resistance in
P. aeruginosa
via gentamicin acetyltransferase I. Like other members of this group, it also confers resistance to Hg
2+
, organomercurials, and certain deoxyribonucleic acid phages. When pMG5 is introduced into a cell carrying a related R factor, some transconjugants can subsequently cotransfer new combinations of resistance determinants as though recombinant plasmids had been formed.
In Vitro Studies with Cefazolin
Authors: Motley Milwood , Shadomy Smith
Published: June 2012

Susceptibilities of 259 isolates of pathogenic bacteria to cefazolin were measured by broth and agar dilution procedures. Beta-hemolytic streptococci were inhibited by 0.25 μg/ml, whereas
Staphylococcus aureus
and alphahemolytic streptococci were inhibited by 2.0 μg/ml. Enterococci were resistant to less than 32 μg/ml. Wide variation was seen with gram-negative species. Most isolates of
Klebsiella
species and
Proteus mirabilis
were inhibited by 4.0 or 8.0 μg/ml.
Escherichia coli
were less susceptible, and most isolates of
Pseudomonas aeruginosa, Serratia
species, and
Enterobacter
species were resistant to 128 μg/ml.
Disk Susceptibility Testing of Slow-Growing Anaerobic Bacteria
Authors: Kwok Yung-Yuan , Tally Francis P. , Sutter Vera L. , Finegold Sydney M.
Published: June 2012

The susceptibility of 55 strains of slow-growing anaerobes to eight clinically useful or potentially useful antibiotics was determined by agar dilution and disk diffusion tests. Strains of the genera
Peptococcus, Peptostreptococcus, Megasphaera, Veillonella, Eubacterium, Bifidobacterium, Clostridium
, and
Fusobacterium
were included. All strains were susceptible to chloramphenicol, but varied in their susceptibility to penicillin, lincomycin, clindamycin, tetracyclines, and vancomycin. Correlation between minimal inhibitory concentration and inhibition zone diameters was generally good. Prediction of susceptibility based on zone diameter measurements appeared satisfactory. Although routine susceptibility testing of anaerobic bacteria is not recommended, there are circumstances where such testing is relevant to the clinical situation. For those laboratories ill-equipped to do dilution tests, a disk diffusion test would give relatively accurate preliminary information. Quantitative susceptibility tests could then be done by a reference laboratory.
Nystatin-Induced Changes in
Saccharomyces cerevisiae
Authors: Venables P. , Russell A. D.
Published: June 2012

Nystatin (5 to 10 μg/ml) was fungicidal to
Saccharomyces cerevisiae
NCYC 361. There was an initial rapid uptake of nystatin by the yeast cells at 30 C, the uptake being pH dependent, with a maximum at low pH values (3 to 4). Photomicrographs indicated that nystatin-treated cells became granular. The effect of growth temperature on the subsequent sensitivity of the yeast cells to nystatin was investigated. Cells grown at 20 C were the most susceptible to all concentrations of nystatin tested; as the pretreatment growth temperature increased, the subsequent uptake of antibiotic by such cells decreased both in intensity and in overall extent, the most marked difference occurring between 20 and 25 C grown cells. Leakage of K
+
and the optical density of suspensions treated with nystatin were similarly affected by growth temperature. Differences in the electrophoretic mobilities of cells grown at different temperatures were also observed. The total ergosterol content of 20 C grown cells was markedly higher than that of 40 C grown cells, with 30 C grown cells having an intermediate value.
Factors Affecting the Production of Candicidin
Authors: Liu Chao-Min , McDaniel L. E. , Schaffner C. P.
Published: June 2012

Factors affecting candicidin synthesis and mycelial growth of
Streptomyces griseus
IMRU 3570 were studied. Inorganic phosphate was found to inhibit candicidin synthesis but to stimulate mycelial growth. Zinc, iron, and magnesium ions stimulated candicidin synthesis at relatively high concentrations in a complex medium but not in a synthetic medium. No other factors studied, such as temperature, oxygen absorption rate, and sugar concentration, were found to differentially affect antibiotic synthesis and mycelial growth. Optimum concentration of inorganic phosphate for candicidin synthesis in a chemically defined medium was found to be between 5 × 10
−5
and 5 × 10
−4
M. The culture in idiophase stage can be reverted to typical trophophase growth by the addition of inorganic phosphate, suggesting the controlling role of inorganic phosphate in repression and derepression of secondary metabolic and primary metabolic activity of the culture. With a soya peptone-glucose medium, the maximum rate of candicidin production could be maintained and extended for a considerable length of time by controlling the culture pH at 8.0, using glucose to adjust the pH during the later stages of a batch fermentation. Carrying out fermentations in this way has given candicidin yields up to 4 g/liter.
BL-S 640, a Cephalosporin with a Broad Spectrum of Antibacterial Activity: Properties In Vitro
Authors: Leitner F. , Buck R. E. , Misiek M. , Pursiano T. A. , Price K. E.
Published: June 2012

BL-S 640 was evaluated in vitro by comparison with cephalothin, cephaloridine, cefazolin, and cephalexin. The new compound was more active than the control cephalosporins against most major gram-negative and some gram-positive species. Moreover, its antibacterial spectrum included strains of
Enterobacter, Proteus morganii, P. rettgeri
, and
Providencia stuartii
, species generally resistant to the other cephalosporins. BL-S 640 was an effective bactericidal agent for strains of various species of
Enterobacteriaceae
. In human plasma, the compound was 58% protein bound.
BL-S640, a Cephalosporin with a Broad Spectrum of Antibacterial Activity: Bioavailability and Therapeutic Properties in Rodents
Authors: Leitner F. , Chisholm D. R. , Tsai Y. H. , Wright G. E. , Deregis R. G. , Price K. E.
Published: June 2012

The bioavailability and therapeutic properties of BL-S 640 in rodents were compared with those of cephalothin, cephaloridine, and cefazolin after parenteral administration, and cephalexin after oral administration. When given intramuscularly in dosages of 5 to 40 mg/kg, peak concentrations of BL-S 640 in the blood of mice were proportional to dose, but when given orally, they were proportional only up to a dose of 25 mg/kg. After either route of administration, the concentration of BL-S 640 in the blood declined at a slower rate than that of the control compounds. Rats receiving BL-S 640 orally excreted an average of 39% of the drug in the urine. BL-S 640 was highly effective in the treatment of mice infected systemically with a variety of pathogenic bacteria, its therapeutic efficacy in comparison with that of other cephalosporins being frequently in excess of what would have been predicted on the basis of comparative activities in vitro.
Bactericidal Activity of Combinations of Gentamicin with Penicillin or Clindamycin Against
Streptococcus mutans
Authors: Snyder Robert J. , Wilkowske Conrad J. , Washington John A.
Published: June 2012

Data derived from testing the bactericidal activity of combinations of penicillin with gentamicin or streptomycin and of clindamycin with gentamicin on nine isolates of
Streptococcus mutans
were analyzed by preparing isobolograms to determine the presence of additive, synergistic, or antagonistic effects. Synergy with penicillin-aminoglycoside combinations was found in two strains; additive effects occurred in seven instances with penicillin-gentamicin combinations; and antagonism occurred in eight instances with clindamycin-gentamicin combinations.
Susceptibility of Clinical Isolates of
Enterobacteriaceae
to BL-S640, a New Oral Cephalosporin
Authors: Watanakunakorn Chatrchai , Bannister Thomas , Glotzbecker Cheryl
Published: June 2012

The in vitro activity of BL-S640, a 7-(2-aryl-2-aminoacetamido)-3-(heterocyclic-thiomethyl) cephalosporin, was evaluated against 338 clinical isolates of
Enterobacteriaceae
in comparison with ampicillin, cephalothin, cefazolin, and cephalexin. Against
Escherichia coli
, BL-S640 was as active as cefazolin and more active than ampicillin, cephalothin, and cephalexin. BL-S640 was as effective as the other cephalosporins tested and far more active than ampicillin against
Klebsiella
and was more active than cephalexin against
Proteus mirabilis
and the indole-positive
Proteus
. The majority of
Enterobacter, Serratia
, and
Citrobacter
were resistant to ampicillin and all the cephalosporins tested. With rare exceptions, the zone of inhibition by the BL-S640 30-μg disk was either larger or the same as the zone obtained by the cephalothin 30-μg disk in the Kirby-Bauer disk susceptibility test.
Pipemidic Acid: Absorption, Distribution, and Excretion
Authors: Shimizu Masanao , Nakamura Shinichi , Takase Yoshiyuki , Kurobe Nobuyuki
Published: June 2012

Pipemidic acid was absorbed well by the oral route. Its peak levels in plasma ranged from 4 to 12 μg/ml at an oral dose of about 50 mg/kg in mice, rats, dogs, monkeys, and men. The protein binding of pipemidic acid was about 20% in dog plasma and about 30% in human serum. Pipemidic acid was distributed to most of the organs and tissues tested at the concentrations comparable to or higher than the plasma level. Its concentrations in bile and urine were much higher than the plasma level. About 25 to 88% of orally administered pipemidic acid was excreted into urine in a bacteriologically active form, the percentage depending on the animals and doses employed. The remainder was excreted into feces in men. The main active principle in vivo was unchanged pipemidic acid itself. The mean lethal dose of pipemidic acid after a single oral dose was more than 16,000 mg/kg in mice. No abnormalities were observed in mice orally receiving pipemidic acid once a day for 4 weeks at doses of 1,000, 2,000, and 4,000 mg/kg per day, and in rats orally receiving the drug once a day for 2 weeks at doses of 400 and 1,600 mg/kg per day.
Laboratory Evaluation of a Rapid, Automated Susceptibility Testing System: Report of a Collaborative Study
Authors: Thornsberry Clyde , Gavan T. L. , Sherris J. C. , Balows Albert , Matsen J. M. , Sabath L. D. , Schoenknecht Fritz , Thrupp L. D. , Washington J. A.
Published: June 2012

Seven laboratories participated in a collaborative study to evaluate the Autobac 1 system. Results obtained with this assay system were compared to those obtained by the standardized Bauer-Kirby disk diffusion test, and each of these two methods was compared to the agar dilution technique. Comparison of the Autobac 1 and the disk diffusion results from the seven laboratories showed an overall average of 91.5% interpretive agreement with the 17 antimicrobial agents tested. The distribution in the levels of Autobac 1/disk diffusion agreement was such that with 13 antimicrobial drugs agreement was 90% or higher; with three, between 85 and 90%; and with one, 77% (nitrofurantoin). Comparison of the Autobac 1 and disk diffusion tests with the International Collaborative Study agar dilution test showed that both methods gave levels of agreement with the International Collaborative Study agar dilution technique that were generally high and equivalent. The average overall agreement between the agar dilution test and each of the other two methods was approximately 90%. Disagreements that did occur tended to involve organisms that were drug susceptible by the Autobac 1 system but intermediate or resistant by the other two methods. This was in part due to the narrow intermediate interpretive zone of the Autobac 1 test. In reproducibility studies with the Autobac 1 and disk diffusion methods, no significant differences were observed between the interpretive reproducibility of the two methods.
R Factor-Mediated Aminoglycoside Antibiotic Resistance in
Pseudomonas aeruginosa
: a New Aminoglycoside 6′-
N
-Acetyltransferase
Authors: Kawabe Haruhide , Kondo Shinichi , Umezawa Hamao , Mitsuhash Susumu
Published: June 2012

The newly introduced semisynthetic aminoglycoside antibiotics, i.e., 3′,4′-dideoxykanamycin B (DKB), 6′-N-methyl DKB (6′-Me-DKB) and amikacin (AK) have been found to be effective against gram-negative pathogens including
Pseudomonas aeruginosa
, which are resistant to the known aminoglycoside antibiotics. We have demonstrated in our stock cultures two types of
P. aeruginosa
strains resistant to DKB, i.e., (DKB
r
.AK
r
.6′-Me-DKB
s
) and (DKB
r
.AK
s
.6′-Me-DKB
r
) (where r = resistant; s = sensitive). Both groups of strains inactivate the drugs by acetylation. The acetylating enzyme was extracted from GN4925(DKB
r
.AK
s
.6′-Me-DKB
r
) and purified by affinity chromatography. Enzymatic studies of the inactivation reaction and chemical studies of the inactivated products indicated that DKB and 6′-Me-DKB were inactivated by acetylation of the 6′-amino group of the drugs. This enzyme acetylates kanamycin A (KM-A), KM-B, DKB, 6′-Me-DKB, 6′-
N
-methyl kanamycin B, but not KM-C, AK, and gentamicin C
1
. The enzyme is named aminoglycoside 6′-
N
-acetyltransferase 3. Genetic studies of two strains resistant to DKB and 6′-Me-DKB disclosed that the enzyme catalyzing inactivation of both DKB and 6′-Me-DKB was mediated by an R factor, i.e., R
ms167
and R
ms168
, capable of conferring resistance to KM, DKB, and 6′-Me-DKB, in addition to resistance to gentamicin, streptomycin, and sulfanilamide, and resistance to tetracycline, chloramphenicol, streptomycin and sulfanilamide respectively.
Rapid Semiquantitative Testing of Antibiotic Susceptibility: Use of a Multicell Disk Elution System
Authors: McGowan John E. , Ayres Cheryl , Sabath L. D.
Published: June 2012

Semiquantitative data regarding antibiotic susceptibility of bacteria were obtained by measuring the growth of bacteria in several different compartments (“cells”) of a plastic module. Each compartment contained an inoculum of the organism and various concentrations of antibiotics in broth, achieved by elution of antibiotic from paper disks placed into the individual cells. Growth of the organisms was measured using an automated monitor to detect the scattering of light. Susceptibility of 300 strains of gram-negative bacilli to multiple concentrations of nine antibiotics was determined by this disk elution system, and the results (expressed in terms of four clinical susceptibility groupings) were compared with those obtained by a quantitative agar dilution method. Results obtained by the two methods agreed completely in 78% of the 2,700 determinations. In evaluating whether individual strains would be susceptible to systemic therapy or not, results obtained by the two systems agreed in all except 149 of the tests. Results of testing by the disk elution method were available on the same day that testing was begun. A system of this type may prove useful, for it provides information of a semiquantitative nature and decreases the time between isolation of a bacterial pathogen and availability of susceptibility data to the clinician.
Effect of Calcium and Magnesium Ions on the Susceptibility of
Pseudomonas
Species to Tetracycline, Gentamicin Polymyxin B, and Carbenicillin
Authors: D'Amato Richard F. , Thornsberry Clyde , Baker Carolyn N. , Kirven Linda A.
Published: June 2012

The effect of calcium and magnesium on the susceptibility of 13 species of
Pseudomonas
to tetracycline, gentamicin, polymyxin B, and carbenicillin was measured. The majority of the minimum inhibitory concentrations (MICs) of these antibiotics was increased if these cations were added to the test media. The increases in MICs caused by calcium or magnesium were similar, but the combination of both ions generally caused a greater change than either alone. Although the MIC of polymyxin B was most affected by calcium and magnesium, its interpretive susceptibilities (i.e., whether susceptible or resistant) were least changed. Susceptibility tests on
Pseudomonas
species probably should be done with Muller-Hinton broth supplemented with physiological concentrations of calcium and magnesium to better approximate the in vivo activity of these antibiotics. When the susceptibility tests were performed with Mueller-Hinton agar, the MICs were slightly less than those obtained with Mueller-Hinton broth supplemented with both cations but greater than those obtained with Mueller-Hinton broth supplemented with individual cations.
In Vivo Protection of
Fusobacterium necrophorum
from Penicillin by
Bacteroides fragilis
Authors: Hackman A. S. , Wilkins T. D.
Published: June 2012

A mixed infection of
Bacteroides fragilis
and
Fusobacterium necrophorum
was resistant to treatment with penicillin even though a pure
F. necrophorum
infection could be successfully treated with penicillin. Since
B. fragilis
alone did not produce infection, these results indicate that
B. fragilis
can protect
F. necrophorum
from penicillin in vivo. The extent of protection afforded by a strain of
B. fragilis
was related to its level of resistance to penicillin. Only a few cells of
B. fragilis
were required in the initial bacterial injection. Moreover, protection was demonstrated when
B. fragilis
cells were injected as late as 24 h after the
F. necrophorum
cells. Protection of
F. necrophorum
from penicillin by
B. fragilis
was also demonstrated in vitro.
Scanning Electron Microscopy of
Candida albicans
After In Vitro Treatment with Miconazole
Authors: De Nollin Sonja , Borgers M.
Published: June 2012

A study was made on the in vitro action of the antimycotic miconazole on
Candida albicans
yeast cells with scanning electron microscopy, and the effects were compared with those seen on the yeast cells by means of transmission electron microscopy. It was found that cells exposed to fungistatic and minimal fungicidal doses of miconazole (10
−7
M and 10
−6
M) presented rough surfaces and had multiple, desoriented buds and bud scars. Whereas in control cultures the cells were well separated, the treated ones formed small clusters of interconnected cells. After exposure to a fungicidal concentration (10
−4
M) of the drug, most of the remaining cells showed smooth surfaces and were covered with numerous vesicular structures probably representing cytoplasmic remnants derived from broken cells. This has been substantiated by the presence of abundant fragments of cell walls and confirmed by examination of similarly treated cultures in the transmission electron microscope. Moreover, the cells with an apparently intact surface when examined with scanning electron microscopy were shown with transmission electron microscopical examination to be completely necrotic inside.
Effects of Cytochalasin B on the Intracellular Bactericidal Activity of Human Neutrophils
Authors: Okuda Kenji
Published: June 2012

Cytochalasin B (CB) is known to have some inhibitory effects on cytokinesis, single-cell movement, bacterial uptake by phagocytes, and many other processes. The effects of CB on intraleukocytic bactericidal activities in human leukocytes were studied, and the results were summarized as follows. (i) CB inhibited the early stage of the intracellular bactericidal activity of human leukocytes against
Streptococcus pyogenes
D58 (group A). The effect was rapidly eliminated by rinsing the CB solution. (ii) In the late stage of the intracellular bactericidal process, however, CB possessed no effect against
S. pyogenes
D58 (group A) and
Staphylococcus aureus
209P. (iii) CB also inhibited the translocation of myeloperoxidase granules to the phagosomes of human neutrophils.
Cycloheximide Production by
Streptomyces griseus
: Control Mechanisms of Cycloheximide Biosynthesis
Authors: Kominek L. A.
Published: June 2012

Cycloheximide accumulation in a fermentation medium has been shown to be the product of the balance between synthesis and degradation of this antibiotic. Glucose has been shown to prevent cycloheximide degradation. Cycloheximide has been shown to interfere with its own synthesis probably due to feedback inhibition. Approaches for increasing cycloheximide titers in the light of these findings are discussed.
Effect of Probenecid on Penetration of Oxacillin into Fibrin Clots In Vitro
Authors: Lee Rachel D. , Brusch John L. , Barza Michael J. , Weinstein Louis
Published: June 2012

Probenecid significantly enhanced the in vitro penetration of oxacillin into fibrin clots suspended in rabbit serum or normal saline.
Pharmacological Evaluation of Amikacin in Neonates
Authors: Howard Jorge B. , McCracken George H.
Published: June 2012

The in vitro bacterial susceptibilities and pharmacokinetic properties of amikacin (BB-K8) were studied in newborn infants. Gram-negative bacteria and
Staphylococcus aureus
isolated from neonates were uniformly susceptible to 10 μg or less of amikacin per ml, and five
Escherichia coli
strains resistant to kanamycin were inhibited and killed by 5 μg or less of amikacin per ml. Mean peak serum concentrations of 17 to 20 μg/ml were observed 30 min after 7.5-mg/kg amikacin doses, and accumulation of drug in serum was not detected after repeated doses for 5 to 7 days. Intravenous infusion of amikacin over a 20-min period resulted in extremely low peak serum levels in four of eight infants studied. Serum half-life values were correlated inversely with postnatal age and renal clearances of amikacin. The volumes of drug distribution indicate that amikacin remains primarily in the extracellular fluid space of neonates. The lack of efficacy and safety data preclude the use of amikacin in neonates at this time.