bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Polymyxin B on Antibiotic-Resistant
Proteus mirabilis
Authors: Sud Inder Jit , Feingold David S.
Published: June 2012

The surface properties of polymyxin B-resistant
Proteus mirabilis
are markedly altered by the antibiotic. The effects include the development of susceptibility to surface-active agents such as deoxycholate or tris(hydroxymethyl)aminomethane and a marked increased osmotic fragility. However, cell wall impermeability to various agents such as erythromycin, actinomycin D, bacitracin, lysozyme, and triphenyltetrazolium chloride apparently remains intact. These results support the concept that the actions of the polymyxins on gram-negative bacteria are multiple; the action(s) of the antibiotic responsible for lethality in vitro, presumably at the level of the cytoplasmic membrane, may represent only a portion of the potential therapeutic effects of the antibiotic in vivo.
Effect of the Removal of Outer Cell Wall Layers on the Actinomycin Susceptibility of a Gram-Negative Bacterium
Authors: MacAlister T. J. , Costerton J. W. , Cheng K.-J.
Published: June 2012

Removal of the outer cell wall layers of a gram-negative marine pseudomonad (B-16) showed that these cells are penetrable by actinomycin D and that, therefore, neither the cytoplasmic membrane nor the peptidoglycan layer constitutes the barrier which excludes this antibiotic from intact cells, but that this barrier is formed by the outer layers of the cell wall which include the lipopolysaccharide component and the double-track layer.
In Vitro and In Vivo Evaluation of Ceftezole, a New Cephalosporin Derivative
Authors: Nishida Minoru , Murakawa Takeo , Kamimura Toshiaki , Okada Naohiko , Sakamoto Hiroshi , Fukada Shigemi , Nakamoto Shoji , Yokota Yoshiko , Miki Kazuyo
Published: June 2012

Ceftezole, a new cephalosporin derivative, was compared with cefazolin, cephaloridine, and cephalothin. Data obtained indicate that it is a broad-spectrum antibiotic, with almost identical antimicrobial activity against pathogenic organisms isolated from patients. The therapeutic effect of ceftezole on experimental infections in mice was similar to that of cefazolin and was superior to that of cephalothin. The binding of ceftezole to serum proteins was somewhat less than that of cefazolin. The concentrations of ceftezole in the sera of test animals and human volunteers were determined after intramuscular injection of 20 mg/kg and after a single dose of 500 mg, respectively. The concentration of ceftezole in the serum of volunteers peaked at 24.9 μg/ml 15 min after injection and remained effective (about 2.6 μg/ml) at 4 h. The half-life in serum under the same conditions was 56 min, i.e., about one-half that of cefazolin. The 24-h urinary recovery rate was 87.5%. Most of the administered ceftezole was excreted unchanged mainly through the urinary tract. The biliary excretion rate in SD strain rats after intramuscular injection of 20 mg/kg was about 4.4%. As compared with commercially available cephalosporins, ceftezole was second only to cefazolin in biliary excretion rate. Various tissue levels of ceftezole in animals were higher than cephalothin but, with the exception of renal levels in the early stage after administration, were lower than cefazolin.
In Vitro Comparison of Netilmicin, a Semisynthetic Derivative of Sisomicin, and Four Other Aminoglycoside Antibiotics
Authors: Kabins S. A. , Nathan C. , Cohen S.
Published: June 2012

One hundred isolates of
Pseudomonas
and
Enterobacteriaceae
, of which 85 were chosen because of their resistance to gentamicin or amikacin, were tested for susceptibility to netilmicin (SCH 20569), a new semisynthetic derivative of sisomicin, and to four other aminoglycosides. Tests were performed in Mueller-Hinton agar and, with 43 of these isolates, also in Mueller-Hinton broth. Most isolates of
Escherichia coli, Klebsiella, Enterobacter, Citrobacter
, and
Serratia
that were gentamicin resistant proved to be susceptible to netilmicin and amikacin. Tests of representative isolates of this group showed that they owed their resistance to the production of aminoglycoside-adenylylating enzymes. Four isolates of
Serratia
, detected by their resistance to amikacin, were also highly resistant to netilmicin but were susceptible to gentamicin. These isolates produced aminoglycoside-acetylating enzymes. Gentamicin-resistant
Proteus
and
Providencia
were, in general, highly resistant to netilmicin but were susceptible to amikacin. These isolates also produced aminoglycoside-acetylating enzymes. Most gentamicin-resistant strains of
Pseudomonas
were resistant to netilmicin, either by enzymatic aminoglycoside modification or by other undefined mechanisms. Thus, like amikacin, netilmicin extends the aminoglycoside susceptibility pattern of
Enterobacteriaceae
to include gentamicin-resistant isolates that produce aminoglycoside-adenylylating enzymes. It is ineffective against strains, some of them susceptible to amikacin, gentamicin, or tobramycin, that produce aminoglycoside-acetylating enzymes.
Phleomycin-Induced Solubilization of Deoxyribonucleic Acid in Uninfected and T Bacteriophage-Infected
Escherichia coli
B
Authors: Shive Karen , Earhart C. F.
Published: June 2012

Phleomycin (PM) induces rapid solubilization of deoxyribonucleic acid (DNA), inhibition of cellular mass increase, and loss of viability when added either to growing cultures of
Escherichia coli
B or an endonuclease I-defective derivative of B. Nonetheless, bacteriophage of the T-even series are produced, albeit to a reduced extent, when PM is added with phage or after infection to
E. coli
cells. Bacteriophage T4 infection inhibits the ability of PM to bring about the solubilization of DNA; this effect appears to account for most of the resistance of T-even phage replication to PM. The patterns of inhibition of phage yields obtained when PM is added at infection suggest that glucosylation of T-even phage DNA may also have a protective effect. However, PM induces the solubilization of glucosylated and nonglucosylated DNA at approximately the same rate and thermal denaturation studies indicate that the antibiotic binds both types of DNA equally well. The latter experiments also provided evidence that PM dissociates from DNA at temperatures greater than 80 C.
In Vitro Effects of Low Concentrations of Penicillin and Sulfadiazine on
Streptococcus mutans
Authors: Weld H. G. , Sandham H. J.
Published: June 2012

Investigations were conducted to determine the in vitro effects of low levels of penicillin and sulfadiazine on the growth, plaque formation, and agglutination of
Streptococcus mutans
and on the synthesis and activity of enzymes synthesizing extracellular polymers. The concentrations tested were equivalent to those expected in the saliva of subjects receiving oral therapy with the agents. Penicillin at 0.5 ng/ml and sulfadiazine at 1 μg/ml substantially inhibited in vitro plaque formation. At these concentrations, sulfadiazine but not penicillin also inhibited growth of the organism. Neither antimicrobial agent affected the agglutination of
S. mutans
with dextran or the synthesis or activity of enzymes synthesizing extracellular polymers. The effect of sulfadiazine on plaque formation was attributed, at least in part, to the inhibitory action of that agent on
S. mutans
growth.
Comparative Activity In Vitro of Ticarcillin, BL-P1654, and Carbenicillin
Authors: Eickhoff Theodore C. , Ehret Josephine M.
Published: June 2012

The activity of ticarcillin, BL-P1654, and carbenicillin was compared in vitro using a microtiter tube dilution test in Mueller-Hinton broth against 50 recent clinical isolates each of
Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella
species,
Enterobacter
species,
Proteus
species, and
Pseudomonas aeruginosa
. Bactericidal end points were determined using a modified Steers replicator. Ticarcillin was generally two to four times more active against all organisms tested except
S. epidermidis
against which BL-P1654 was most active. Median minimum inhibitory concentrations in micrograms per milliliter were for
S. aureus
: ticarcillin (6.2), carbenicillin (12.5), BL-P1654 (25); for
S. epidermidis
: BL-P1654 (1.6), ticarcillin (3.2), carbenicillin (3.2); for
E. coli
: ticarcillin (3.2), BL-P1654 (6.2), carbenicillin (6.2); for
Klebsiella
sp.: >100 for all three drugs; for
Enterobacter
sp.: ticarcillin (3.2), carbenicillin (6.2), BL-P1654 (12.5); for
Proteus
sp.: ticarcillin (1.6), carbenicillin (1.6), BL-P1654 (3.2); for
P. aeruginosa
: ticarcillin (31), BL-P1654 (62), carbenicillin (125). Bactericidal end points were dependent on both the drug and the species but were in general no more than twofold more than the minimum inhibitory concentration with the exception of BL-P1654 against
P. aeruginosa
. BL-P1654 was bactericidal for only 60% of the strains tested at a concentration of 500 μg/ml.
Treatment of Murine Coccidioidomycosis with Polymyxin B
Authors: Collins M. S. , Pappagianis D.
Published: June 2012

An agar dilution method was employed to test the susceptibility of 12 strains of
Coccidioides immitis
to polymyxin B (PB). After 3 days of incubation, eight strains were markedly inhibited by 5.0 μg of PB per ml and four strains did not grow. PB at 10 μg/ml inhibited the growth of all strains through 20 days of incubation. To determine whether PB has anticoccidioidal activity in vivo, mice in groups of 30 were infected intraperitoneally with a mean lethal dose (LD
50
) or 20 LD
50
of arthrospores of
C. immitis
ATCC 28868 (Silveira). Treatment by intraperitoneal injection of PB (2.5 mg/kg) was begun 2 or 5 days after challenge. By 40 days after infection, 47 and 7% of the untreated mice challenged with an LD
50
, respectively, were alive. Of mice infected with an LD
50
or 20 LD
50
and treated with PB beginning 2 days after the challenge, 90% of each group were alive by day 40. Initiation of PB therapy 5 days after infection permitted survival of 84% of the mice infected with an LD
50
; however, only 27% of the mice infected with 20 LD
50
survived by day 40. In this latter group there was evidence that PB prolonged life since 56% of the treated mice were alive by day 15 as compared with 30% of the controls. PB in vivo was fungistatic since the majority of treated mice had
C. immitis
in the liver, lungs, and spleen.
Formation of Methylated and Phosphorylated Metabolites During the Fermentation Process of Verdamicin
Authors: Lee B. K. , Condon R. G. , Wagman G. H. , Weinstein M. J.
Published: June 2012

In an attempt to understand the biosynthetic processes leading to the formation of verdamicin (end product), we have examined the patterns of the formation of methylated and phosphorylated metabolites, which resulted from either the addition of
l
-[
methyl
-
14
C]methionine or [
32
P]KH
2
PO
4
to the fermentation. Incorporation of label from
l
-[
methyl
-
14
C]methionine into the bioactive sisomicin, verdamicin, and the chromatographically polar components increased with the progression of time. Two methylated bioinactive metabolites were found in the culture broth after removal of the methylated bioactive metabolites. In contrast to the bioactive metabolites, incorporation of the
methyl
-
14
C label into the two methylated bioinactive metabolites decreased with the progression of time. A phosphorylated bioinactive metabolite (nonmethylated) was also found in the culture broth, fermented in the presence of [
32
P]KH
2
PO
4
. The role of the phosphorylated metabolite in the biosynthesis of the bioactive metabolites cannot yet be explained.
Activity of Newer Aminoglycosides and Carbenicillin, Alone and in Combination, Against Gentamicin-Resistant
Pseudomonas aeruginosa
Authors: Marks M. I. , Hammerberg S. , Greenstone G. , Silver Barry
Published: June 2012

The in vitro activity of the aminoglycoside antibiotics tobramycin, sisomicin, amikacin, gentamicin, and netilmicin (SCH 20569) were compared against 26 gentamicin-resistant isolates of
Pseudomonas aeruginosa
cultured from hospitalized children. Tobramycin had the greatest activity on a weight basis, followed by sisomicin, gentamicin, amikacin, and netilmicin. All isolates were resistant to achievable concentrations of netilmicin and gentamicin, but 23% were inhibited by achievable concentrations of tobramycin, 8% by amikacin, and 4% by sisomicin. The combinations carbenicillin/tobramycin, carbenicillin/sisomicin, and carbenicillin/amikacin were synergistic for 92% of strains; antagonism was not encountered. These in vitro results suggest that tobramycin, sisomicin, or amikacin in combination with carbenicillin would be the safest initial regimen in the therapy of gentamicin-resistant
Pseudomonas
infections pending susceptibility studies.
Comparison of Thrombophlebitis Associated with Three Cephalosporin Antibiotics
Authors: Siebert W. T. , Westerman E. L. , Smilack J. D. , Bradshaw M. W. , Williams T. W.
Published: June 2012

A double-blind study with volunteers was performed to determine the incidence and severity of thrombophlebitis associated with cephalothin, cephapirin, cefamandole, and a water control. Although there were no statistical differences in the incidence of thrombophlebitis, cephalothin resulted in significantly more severe thrombophlebitis compared with the other agents.
Effect of Organic Mercurials and Sulfhydryl Compounds on the Urease Activity of
Proteus
: Inhibition by Urine and Ascorbic Acid
Authors: Kunin Calvin M.
Published: June 2012

Meralluride, mercaptomerin, ethacrynic acid, and penicillamine inhibited urease activity of
Proteus mirabilis
. The activity of the organic mercurials and ethacrynic acid was markedly inhibited by human and dog urine. Antiurease activity could not be detected in the urine of a human and a dog given meralluride by injection. Urine from patients receiving penicillamine also failed to inhibit urease activity. Ascorbic acid inhibited, whereas dehydroascorbic acid enhanced, the activity of the mercurials, but neither agent altered the inhibitory effect of urine. The lethal effect of meralluride against
Proteus
occurred at the same concentration at which urease activity was inhibited, but penicillamine inhibited the enzymatic activity without affecting viability of the organism. The data suggest that these sulfhydryl-reactive compounds will not be useful against
Proteus
infections of the urinary tract.
In Vitro Study of Netilmicin Compared with Other Aminoglycosides
Authors: Fu Kwung P. , Neu Harold C.
Published: June 2012

Netilmicin (Sch 20569) is an ethyl derivative of gentamicin C
1a
that is active against most
Enterobacteriaceae, Pseudomonas aeruginosa
, and
Staphylococcus aureus
isolates. Among 342 clinical isolates tested, all staphylococci; 92% of
Escherichia coli
, 93% of
Klebsiella pneumoniae
, and 92% of
Enterobacter
were inhibited by 0.8 μg or less of netilmicin per ml, but only 78% of
P. aeruginosa
were inhibited by 3.1 μg or less per ml. Most clinical isolates of enterococci,
Serratia marcescens
, and
Providencia
were not inhibited by 3.1 μg of netilmicin per ml. Like other aminoglycosides, the netilmicin in vitro activity was markedly influenced by the growth medium used, with activity decreased by sodium, calcium, and magnesium. Netilmicin was more active at alkaline pH. Addition of magnesium to
Pseudomonas
or
Serratia
pretreated with netilmicin produced inhibition of killing. Netilmicin was more active than gentamicin, sisomicin, tobramycin, or amikacin against
E. coli
and
K. pneumoniae
. Netilmicin inhibited growth of all gentamicin-resistant isolates of
Klebsiella
and
Citrobacter
tested, but only 73% of
E. coli; Pseudomonas
and
Providencia
were resistant to netilmicin. Most
Serratia
(95%) and indole-positive
Proteus
(83%) isolates were resistant to netilmicin but were inhibited by amikacin.
Synergy of Mecillinam, a Beta-Amidinopenicillanic Acid Derivative, Combined with Beta-Lactam Antibiotics
Authors: Neu Harold C.
Published: June 2012

Mecillinam, a β-amidinopenicillanic acid derivative, was combined with ampicillin, amoxicillin, carbenicillin, cephalothin, cefamandole, and cefoxitin and tested against most members of the
Enterobacteriaceae
and
Pseudomonas
. Synergy was demonstrated with selected isolates of most of the organisms tested. Isolates highly susceptible to mecillinam (minimum inhibitory concentration, <0.8 μg/ml) were not synergistically inhibited by addition of another β-lactam antibiotic. Synergy of mecillinam and a β-lactamase-resistant penicillin, cloxacillin, was demonstrated. In media of osmolality >10 mOsm or of conductivity >6 mS, mecillinam and β-lactam antibiotics showed synergy in most instances, whereas at low osmolality and conductivity the activity of mecillinam is so great that synergy cannot be demonstrated. The proportion of mecillinam to β-lactam antibiotic that will be synergistic ranged from 100:1 to 1:1 to 1:100. Mecillinam did not increase the activity, minimum inhibitory concentration or minimum bactericidal concentration values, of β-lactam compounds against streptococci, staphylococci, clostridia, listeria, or bacteroides. Synergy was not demonstrated with combinations of mecillinam and aminoglycosides (kanamycin, gentamicin, tobramycin, amikacin), chloramphenicol, tetracycline, or polymyxins.
5″-Amino-5″-Deoxybutirosin, a Semisynthetic Analogue of Butirosin A: Antibacterial Activity In Vitro and in Mice
Authors: Heifetz C. L. , Frey C. A. , Pearson I. A. , Sesnie J. C.
Published: June 2012

Aminodeoxybutirosin (AD-BTN), the 5″-amino-5″-deoxy derivative of butirosin (BTN), was synthesized to improve on the antibacterial activity of BTN by preventing bacterial enzymatic phosphorylation at the 5″ position. AD-BTN possesses the spectrum characteristic of BTN and gentamicin (GTM) and was active at low levels in vitro against a wide variety of gram-negative species including
Pseudomonas aeruginosa
, indole-positive
Proteus
and
Serratia marcescens
; its action was bactericidal against both light and heavy inocula, and it was not antagonized by human serum. AD-BTN was as active as GTM against GTM-sensitive
P. aeruginosa
in vitro and in mice, and was markedly improved over BTN. AD-BTN retained the good activity of the parent compound against other gram-negative pathogens. Whereas GTM minimal inhibitory concentrations were elevated 35-fold against GTM-resistant
P. aeruginosa
in vitro, the minimal inhibitory concentration of AD-BTN was only doubled. At 6.3 μg/ml, AD-BTN inhibited 68% of 82 isolates insusceptible to that concentration of GTM. In murine toxicity tests AD-BTN was about one-third to one-half as toxic as GTM.
Multiple Antibiotic Resistance in Clinical Strains of
Neisseria gonorrhoeae
Isolated in South Carolina
Authors: Powell James T. , Bond John H.
Published: June 2012

Minimal inhibitory concentration (MIC) values for penicillin G, tetracycline, amoxicillin, and actinomycin D were determined for 81 strains of
Neisseria gonorrhoeae
isolated from patients attending public health clinics in the Piedmont region of South Carolina. Gonococcal isolates were also screened for highlevel resistance to streptomycin. Significant positive correlations (
r
≥ 0.45,
P
≤ 0.01) were found between all possible pairs of the antibiotics penicillin G, tetracycline, and amoxicillin. The MIC values of actinomycin D showed no significant positive correlations with the MIC values of the other antibiotics. Gonococcal strains that were resistant to streptomycin tended to be resistant to penicillin G, tetracycline, and amoxicillin. Of the 81 isolates, 18.5% were multiply resistant to penicillin G, tetracycline, amoxicillin, and streptomycin. Spontaneous mutants with reduced antibiotic susceptibility, selected for decreased susceptibility to penicillin G, displayed small decreases in susceptibility to tetracycline, amoxicillin, and actinomycin D. Spontaneous mutants selected for decreased susceptibility to actinomycin D displayed small losses in susceptibility to penicillin G. The results show that multiple antibiotic resistance occurs in clinically isolated gonococcal strains in South Carolina. The results further suggest the presence of a common genetic mechanism determining antibiotic resistance in
N. gonorrhoeae
.
Comparative Toxicological Studies of Amphotericin B Methyl Ester and Amphotericin B in Mice, Rats, and Dogs
Authors: Keim G. R. , Sibley P. L. , Yoon Y. H. , Kulesza J. S. , Zaidi I. H. , Miller M. M. , Poutsiaka J. W.
Published: June 2012

In acute and subacute toxicological studies, amphotericin B methyl ester was shown to be much less toxic than the parent antibiotic. As a single intravenous dose in mice, the methyl ester was approximately 20 times less toxic than amphotericin B. Also, the acute toxicity of the methyl ester in mice was not enhanced by the presence of chemically induced hepatic or renal damage or by the concurrent administration of amphotericin B or flucytosine. In a 1-month intraperitoneal study in rats, the methyl ester was about one-fourth as nephrotoxic as amphotericin B. In a 1-month intravenous study in dogs, the methyl ester was about one-eighth as nephrotoxic and one-fourth to one-half as hepatotoxic as the parent compound. In addition, the methyl ester, unlike amphotericin B, produced minimal renal effects, which did not increase in severity with increasing dosage. Based on the results of these studies, it is concluded that amphotericin B methyl ester has the potential for an improved therapeutic ratio in the treatment of systemic mycoses.
Therapeutic Effects of Small-Particle Aerosols of Ribavirin on Parainfluenza (Sendai) Virus Infections of Mice
Authors: Larson E. W. , Stephen E. L. , Walker J. S.
Published: June 2012

Small-particle aerosol administration of ribavirin (1-β-
d
-ribofuranosyl-1,2,4-triazole-3-carboxamide) increased survival rates, extended the time to death, delayed lung pathology, and reduced pulmonary virus levels in Sendai virus-infected mice.
Josamycin and Rosamicin: In Vitro Comparisons with Erythromycin and Clindamycin
Authors: Shadomy Smith , Tipple Margaret , Paxton Larry
Published: June 2012

The macrolide antibiotics josamycin and rosamicin were compared in vitro with erythromycin for activity against
Staphylococcus aureus, S. epidermidis
, and enterococci and with clindamycin for activity against a variety of anaerobic organisms. Rosamicin and erythromycin were similar in activity and superior to josamycin against aerobic cocci. Most isolates of
S. aureus
(96%),
S. epidermidis
(79%), and the enterococci (87%) were inhibited by 1.56 μg of either of the new macrolide compounds per ml. Clindamycin was the most active compound against the anaerobic organisms.
Inhibition of Multiplication of
Mycobacterium leprae
by Polyinosinic-Polycytidylic Acid
Authors: Levy Louis , Merigan Thomas C.
Published: June 2012

Contrary to the results of an earlier study in which polyinosinic-polycytidylic acid [poly(I:C)] administered intraperitoneally to mice had no effect on multiplication of
Mycobacterium leprae
in the mouse footpad, the local administration of poly(I:C) every 12 h for 15 doses during logarithmic multiplication was found both to inhibit bacterial multiplication and to produce high tissue levels of interferon (IF). Local administration of poly(I) alone inhibited multiplication of
M. leprae
to almost as great a degree without at the same time producing a measurable IF titer in the footpad tissues. Mouse IF and “mock” IF both inhibited bacterial multiplication to the same degree, but administration of only the former resulted in a measurable IF titer. Polyadenylic-polyuridylic acid administered locally neither inhibited multiplication nor induced IF; fetal calf serum, administered in the same concentration as found in the preparations of IF and mock IF, was modestly inhibitory, without inducing IF. Thus, the local administration of poly(I:C) appears to have inhibited multiplication of
M. leprae
independently of IF induction.
Mechanisms of Gentamicin Resistance in
Staphylococcus aureus
Authors: Dowding J. E.
Published: June 2012

Three clinical isolates of
Staphylococcus aureus
resistant to gentamicin and other aminoglycosides have been examined for antibiotic modifying enzymes. The strains contain a number of these enzymes, most of them similar to those commonly found in aminoglycoside-resistant gram-negative strains. All three strains (and a transductant derived from one of them) contain two enzymes mediating gentamicin resistance, an aminoglycoside 6′-
N
-acetyltransferase and a novel enzyme, gentamicin phosphotransferase.
Requirements of Glucose and Incubation Under Static Conditions for Optimal Colicin E1 Induction
Authors: Nakazawa Atsushi , Suzuki Nobuo , Tamada Terumi
Published: June 2012

A rapid rate and large amounts of colicin E1 synthesis were induced by incubating colicinogenic cells without aeration in the presence of glucose. The decrease in ability of colicin induction by aeration was not due to an ample supply of oxygen, but to the simple agitation of the bacterial suspension. Sugars other than glucose that support colicin synthesis were mannose, fructose, glucose-6-phosphate, and mannitol. The effect of sugars in mutants deficient in enzymes of glucose metabolism suggested that some intermediary metabolites between glucose and pyruvate are closely related to the stimulation of colicin synthesis under these conditions. Analyses of deoxyribonucleic acid replication indicated that the induced replication of the colicin E1 plasmid deoxyribonucleic acid occurred even under conditions in which colicin was not actively synthesized.
Microdilution Transfer Plate Technique for Determining In Vitro Synergy of Antimicrobial Agents
Authors: Dougherty Paula F. , Yotter David W. , Matthews Thomas R.
Published: June 2012

A microdilution transfer plate technique for determining in vitro synergy of antimicrobial agents is described. Combinations of gentamicin-nalidixic acid against
Proteus mirabilis
and rifampin-amphotericin B against
Candida albicans
are used as examples to demonstrate the technique. Results correlate with published data obtained by conventional methods. The technique is effective for evaluating the in vitro effects of antimicrobial agent combinations against both bacteria and fungi. The technique enables one to produce a checkerboard gradient in a fast, convenient, and reproducible way; results are easily visualized.
Simple, Direct Broth-Disk Method for Antibiotic Susceptibility Testing of
Ureaplasma urealyticum
Authors: Spaepen Moniek S. , Kundsin Ruth B.
Published: June 2012

A simple, direct broth-disk test, utilizing urine sediment as the inoculum and impregnated paper disks as the source of antibiotic, was developed and used to test the susceptibility of 54 isolates of
Ureaplasma urealyticum
(T-strain mycoplasmas) to minocycline, doxycycline, demeclocycline, tetracycline, and erythromycin. The concentration of each antibiotic was calculated to approximate the attainable blood level. Resistance or susceptibility to each antibiotic was determined by growth, indicated by a color change of the medium in each tube, comparable to that of a control culture without antibiotic. Of the 54 T-mycoplasmas tested, 46 (85.2%) were inhibited by 1 μg of minocycline per ml, 45 (83.3%) were inhibited by 1 μg of doxycycline per ml, 38 (72.2%) were inhibited by 1 μg of demeclocycline per ml, 18 (33.3%) were inhibited by 1 μg of tetracycline per ml, and only 2 (3.7%) were inhibited by 3 μg of erythromycin per ml. Seven (13%) of the 54 T-mycoplasmas tested were resistant to all five antibiotics. There was good correlation between results obtained by this direct broth-disk method and minimal inhibitory concentrations obtained by the direct broth dilution method.
Lethal and Mutagenic Effects of 5-Iodouracil on Bacteriophage T4
td
8
r
II
Authors: Byrd Daniel M. , Prusoff William H.
Published: June 2012

Evidence was obtained which indicates that the lethal effect of 5-iodouracil (IUra) on bacteriophage T4 is not due to a mutagenic process. T4
td
8
r
II (thymine requiring, rapid lysis) double mutants were constructed. Reversion of T4
td
8
r
II to
r
+
was measured. First, reversion by growth in the presence of the structural analogues chlorouracil (ClUra) and bromouracil (BrUra) did not correlate with their relative lethal effects (for mutagenesis: IUra ≤ ClUra ≤ BrUra; for lethality: ClUra < BrUra < IUra). Second, reversion frequencies of T4
td
8
r
II in infected cells increased linearly with time of growth in the presence of IUra, whereas the frequency of lethality was constant with time. Third, reversion frequencies increased markedly at low levels of IUra substitution, whereas lethal effects were apparent only with extensive IUra substitution. Fourth, the reversion frequency of the nonviable fraction of IUra-substituted T4
td
8
r
II (as examined by multiplicity reactivation) did not differ significantly from that of the viable IUra-substituted T4
td
8 fraction. If mutagenesis caused lethality, then the nonviable T4
td
8
r
II fraction should accumulate mutations and have a higher reversion frequency.
Antibiotic Metabolites from a Marine Pseudomonad
Authors: Wratten Stephen J. , Wolfe Margaret S. , Andersen Raymond J. , Faulkner D. John
Published: June 2012

An antibiotic-producing pseudomonad was isolated from a seawater sample from a La Jolla, Calif., tidepool. The pseudomonad produces two novel antibacterial compounds, 2-
n
-pentyl-4-quinolinol and 2-
n
-heptyl-4-quinolinol. It also synthesizes indole-3-carboxaldehyde, 6-bromoindole-3-carboxaldehyde, and the known antibiotic
p
-hydroxybenzaldehyde. Each of these compounds was identified by analysis of spectral data, and the structures were confirmed by synthesis or comparison with authentic samples.
Resistance Plasmid Transfer by
Serratia marcescens
in Urine
Authors: Schaberg Dennis R. , Highsmith Anita K. , Wachsmuth Ina K.
Published: June 2012

Resistance plasmids were transferred in urine from a multi-drug-resistant
Serratia marcescens
to
Escherichia coli
. Transfer of resistance to kanamycin, tetracycline, chloramphenicol, streptomycin, ampicillin, and carbenicillin occurred readily after 4 h of incubation at room temperature (25°C). The urinary catheter collection bag is postulated as a potential site for extraintestinal resistance plasmid transfer in the
Enterobacteriaceae
, especially for pathogens such as
Serratia
, which do not frequently colonize the intestinal tract.
Netilmicin and Gentamicin: Comparative Pharmacology in Humans
Authors: Riff Louise J. , Moreschi Gail
Published: June 2012

Thirteen male subjects received 1 mg of either gentamicin or netilmicin per kg, first intramuscularly and then intravenously. After the intramuscular dose, concentrations of gentamicin in the serum were more variable than those of netilmicin. After the intravenous dose, the distribution phase of netilmicin was twice as rapid as gentamicin. The average half-times of the elimination phase were similar, but there was marked variability among the subjects receiving gentamicin. Serum clearance of netilmicin was more rapid than that of gentamicin and could not be attributed to renal elimination. The data indicate that, after intramuscular administration, netilmicin may produce more predictable blood levels than gentamicin and suggest that the body distribution of netilmicin may differ from that of gentamicin.
Assay of Gentamicin in Serum by High-Pressure Liquid Chromatography
Authors: Anhalt John P.
Published: June 2012

A procedure is described that uses high-pressure liquid chromatography for assay of gentamicin in serum. The technique involves extraction of gentamicin from serum by using a CM-Sephadex column and analysis by reverse-phase, ion-pair chromatography. Continuous-flow, post-column derivatization with
o
-phthaladehyde is used to form fluorescent products for detection. The possible scope of this method for analysis of other aminoglycoside antibiotics is illustrated by application to sisomicin and netilmicin.
Susceptibility of Clinical Isolates of Cytomegalovirus to Human Interferon
Authors: Postic Bosko , Dowling John N.
Published: June 2012

Human cell culture-derived interferon was shown to inhibit human cytomegalovirus in vitro. A prototype strain, Davis, and six clinical isolates of cytomegalovirus were tested. All six isolates showed uniform susceptibility to interferon, exceeding that of the Davis strain by two- to fourfold. The latter virus was found to be 32 to 4 times less susceptible than the sensitive indicator, vesicular stomatitis virus. However, the laboratory finding of susceptibility to an antiviral material may not relate to its clinical effectiveness.
Comparative Susceptibility of Anaerobic Bacteria to Ticarcillin, Cefoxitin, Metronidazole, and Related Antimicrobial Agents
Authors: Henderson David K. , Chow Anthony W. , Guze Lucien B.
Published: June 2012

The in vitro antimicrobial activity of two newer agents, ticarcillin and cefoxitin, against 204 recent clinical isolates of anaerobic bacteria was determined by an agar dilution technique, and compared to their related compounds carbenicillin, cephalothin, and penicillin, as well as metronidazole, clindamycin, and chloramphenicol. Ticarcillin was similar to carbenicillin, and cefoxitin was more active than cephalothin. At readily achievable blood concentrations of each antimicrobial agent, ticarcillin was slightly less active than clindamycin against
Bacteroides fragilis
. Cefoxitin was superior to cephalothin and penicillin against
B. fragilis
. Penicillin remained highly active against all obligate anaerobes other than
B. fragilis
. Metronidazole, while highly effective against
B. fragilis
and
Clostridium perfringens
, was only intermediately effective against anaerobic gram-positive cocci and relatively inactive against nonsporulating anaerobic gram-positive bacilli. Further evaluation of the clinical efficacy of ticarcillin, carbenicillin, and cefoxitin against anaerobic infections is indicated.
Tobramycin: Maternal-Fetal Pharmacology
Authors: Bernard Betty , Garcia-Cázares Salvador J. , Ballard Charles A. , Thrupp Lauri D. , Mathies Allen W. , Wehrle Paul F.
Published: June 2012

To investigate the maternal-fetal transfer of tobramycin (TBM) and its distribution in the fetus, a single dose of 2 mg/kg was administered intramuscularly to 35 pregnant patients (13 first trimester, 22 second trimester) 0.5 to 34 h before hysterectomy. TBM concentration was assayed microbiologically in maternal serum, fetal tissues (placenta, brain, lung, liver, and kidney), and fluids (amniotic, cerebrospinal fluid [CSF], urine, and serum). Mean maternal serum half-life (1.54 h) and mean peak serum concentration of TBM were within ranges reported for nonpregnant adults. In fetal serum, half-life was 5.2 h, and TBM levels did not exceed 0.58 μg/ml. For intervals up to 34 h, the mean TBM concentration in placental tissues was 1.4 μg/g. Concentration differences related to fetal maturation were found for fetal CSF, amniotic fluid, and fetal kidney. No antimicrobial activity was found in the fetal CSF of >16 weeks' gestation. TBM was present predominantly in the second trimester amniotic fluid specimens. Fetal kidney concentrations reached 7.2 μg/g at 34 h after maternal drug administration. Higher TBM concentrations were related to advanced maturation of the fetal kidney. Second trimester fetal urine concentrations for TBM ranged from 0.1 to 3.4 μg/ml, and the fetal urinary half-life was 3.7 h. Knowledge of fetal pharmacology is essential for weighing the fetal benefits or risks of antimicrobial therapy for the infected gravid patient.
Bacteriocin Production by Strains of
Bacteroides
Isolated from Human Feces and the Role of These Strains in the Bacterial Ecology of the Colon
Authors: Booth S. J. , Johnson J. L. , Wilkins T. D.
Published: June 2012

Several human fecal isolates of
Bacteroides
have been found to produce bacteriocins. The bacteriocin-producing strain T1-1 was studied in the most detail. Strain T1-1 belongs to the 0061-1 deoxyribonucleic acid (DNA) homology group of
Bacteroides
. This homology group phenotypically resembles
Bacteroides thetaiotaomicron
but has little DNA homology with it. The bacteriocin-producing strains T1-12 and T1-48 belong to the 3452-A DNA homology group. This group has DNA homology with
B. thetaiotaomicron
and
Bacteroides ovatus
. The bacteriocin-producing strain T1-42 remains unidentified in that it does not belong to any recognized DNA homology group of the saccharolytic intestinal bacteroides. The extracellular bacteriocin produced by strain T1-1 was specifically bactericidal for other bacteria within the genus
Bacteroides
. The highest bacteriocin titers (32 to 64) were produced in complex media, with only trace amounts being produced in a defined medium. The bacteriocin appeared to have a high molecular weight (≥300,000) and was unusual because it was stable from pH 1 to 12 and only a 50% reduction in activity resulted after 15 min at 121°C in an autoclave. It was inactivated by trypsin and Pronase. Strain T1-1 was isolated from all three fecal samples obtained over a 25-week period from an individual who was part of a National Aeronautics and Space Administration mock Skylab flight. Strains T1-12, T1-48, and T1-42 were isolated only from the first fecal sample. Each of these strains was immune to the bacteriocins produced by the others. These strains were found to coexist in the colon with a larger population of non-bacteriocin-producing, bacteriocin-susceptible strains of
Bacteroides
.
Aggregation-Dependent Changes in Susceptibility of
Dictyostelium discoideum
to Amphotericin B
Authors: Rossomando Edward F. , Hesla Mary Ann , Heitz Mary Ann , Maldonado Barbara
Published: June 2012

In this study, the polyene antibiotic amphotericin B was used to induce changes in permeability and viability of the eucaryotic microorganism
Dictyostelium discoideum
. The results show that as the cells progress from the growth phase through stationary phase to eventual aggregation, they become increasingly resistant to both permeability changes and lysis. Plasma membranes were prepared from cells harvested at exponential growth, stationary phase, and the aggregation-competent stage, and both the neutral lipid and phospholipid content were determined. An increase in the neutral lipid and a decrease in the phospholipid were observed as the cells progressed from growth into aggregation, with the overall result that the phospholipid-sterol ratio decreased during this period. The extent of amphotericin B binding by cells from the different stages was also determined. Aggregation cells exhibited a small but significant increase in binding compared to cells from either of the other two stages. The permeability changes produced by the drug were measured as a function of temperature. Exponentially growing cells showed a marked temperature dependence for the drug effect, whereas aggregating cells did not. Rates of inactivation by the drug were also determined over a range of temperatures. With exponentially growing cells, the rate of inactivation was temperature dependent, whereas with aggregating cells it was not. Finally, drug binding for both growing and aggregating cells was temperature dependent. Thus, no binding was observed for cells of either type at 4°C. This finding suggests that the differences in the temperature dependence of the permeability changes and inactivation between the cells involve parameters other than drug binding.
d
-Cycloserine-Induced Alterations in the Transport of
d
-Alanine and Glycine in
Bacillus subtilis
168
Authors: Clark Virginia L. , Young Frank E.
Published: June 2012

d
-Alanine,
l
-alanine, and glycine transport was investigated in
Bacillus subtilis
168 cells that were phenotypically resistant to
d
-cycloserine. These cells showed enhanced rates of uptake as compared with that observed in sensitive cells. The usual enhancement in
d
-alanine and glycine transport resulting from treatment of the cells with
d
-cycloserine could be prevented by the addition of rifampin. Kinetic analyses of the initial rate of glycine transport indicated an increase in the

V
max

for transport in resistant cells, with no alteration in the

K
m

for glycine. Investigations of the net transport of glycine revealed that resistant cells maintained a higher gradient of glycine than did sensitive cells. Kinetic analyses of the net transport of glycine suggested that a new system for the accumulation of glycine was present in
d
-cycloserine-resistant cells.
Phosphonoacetic Acid-Resistant Mutants of Herpes Simplex Virus: Effect of Phosphonoacetic Acid on Virus Replication and In Vitro Deoxyribonucleic Acid Synthesis in Isolated Nuclei
Authors: Becker Yechiel , Asher Yael , Cohen Yaffa , Weinberg-Zahlering Eynat , Shlomai Joseph
Published: June 2012

Phosphonoacetic acid (PAA) inhibits the replication of herpes simplex virus in BSC-1 cells and the in vitro synthesis of deoxyribonucleic acid (DNA) in isolated nuclei. Phosphonopropionic acid at a concentration of 100 μg/ml had no effect on herpes simplex virus replication. PAA-resistant mutants were obtained at a rate of 1 in 10
4
plaque-forming units after 5-bromodeoxyuridine mutagenization of the virus. These mutants replicate in BSC-1 cells in the presence of 100 μg of PAA per ml and induce a PAA-resistant DNA polymerase that synthesizes DNA in vitro in the presence of PAA.
Transfer of Beta-Lactamase Genes of
Neisseria gonorrhoeae
by Conjugation
Authors: Kirven Linda A. , Thornsberry Clyde
Published: June 2012

Recent isolates of
Neisseria gonorrhoeae
have been shown to be resistant to penicillin because they produce β-lactamase. In this study, conjugal transfer of the β-lactamase gene to a recipient
N. gonorrhoeae
strain occurred in one of the two strains studied but not in the other. The transconjugant could also conjugally transfer the β-lactamase gene to an
Escherichia coli
strain.
Manner and Meaning of Susceptibility Testing of Ampicillin-Resistant
Haemophilus influenzae
Authors: Gray Barry M. , Hubbell Carol A. , Dillon Hugh C.
Published: June 2012

We examined ampicillin-resistant strains of
Haemophilus influenzae
to compare the percentage of resistant organisms in each strain with the susceptibility to ampicillin by an agar dilution method. Using an inoculum of 10
4
colony-forming units, the minimal inhibitory concentration (MIC) increased with the percentage of resistant organisms in the strain. Laboratory-manipulated strains composed of different proportions of a susceptible and a resistant strain behaved similarly. The survival of isolated colony-forming units (colony MIC) was then determined by spreading inocula over the surface of a set of MIC plates, resulting in separation of individual colonies. This modification of the susceptibility test to the colony level gave end points that were clear and reproducible and that did not vary with changes in incubation time or temperature. True differences in susceptibility among strains were demonstrated by this method, whereas results of the conventional MIC test may reflect only the number of resistant organisms present in the inoculum.
Effects of Gestational Age, Birth Weight, and Hypoxemia on Pharmacokinetics of Amikacin in Serum of Infants
Authors: Myers Martin G. , Roberts Robert J. , Mirhij Najwa J.
Published: June 2012

The serum pharmacokinetics of amikacin were studied in 36 infants treated for suspected bacterial infection. A prolonged serum half-life was associated with the related variables of birth at an early gestational age, low birth weight, and hypoxemia. A postnatal age effect was not apparent when hypoxemic infants were excluded.
Induction of Bacteriocins from
Clostridium perfringens
by Treatment with Mitomycin C
Authors: Mahony D. E.
Published: June 2012

Six of ten bacteriocinogenic strains of
Clostridium perfringens
were inducible by treating the cultures with mitomycin C. Induction did not occur in the continued presence of mitomycin C but only when excess mitomycin C was removed. Cell death was associated with induction of bacteriocin.
Cyclic Adenylic Acid-Dependent and -Independent Production of Chloramphenicol Acetyltransferase in
Escherichia coli
Carrying R Plasmids
Authors: Yokota Takeshi , Kuwahara Rie , Hagiwara Sumiko , Kuwahara Shogo
Published: June 2012

A plasmid-specified, inducible, but cyclic adenylic acid (cAMP)-independent resistance to chloramphenicol (CM) is reported. The resistance level to CM was increased two- to fourfold by treatment with a small amount of CM for a short period in
Escherichia coli
strains carrying the R plasmid pJY1, which was obtained from a clinical isolate of
Vibrio cholerae
. Though cAMP was required for production of CM acetyltransferase (CATase) in cAMP-deficient mutants of
E. coli
carrying the R100 plasmid, the same species harboring pJY1 did not require cAMP for production of the enzyme. The possibility of a mechanism other than CATase activity for the CM resistance conferred by R plasmids is discussed.
Auxotypes and Penicillin Susceptibilities of
Neisseria gonorrhoeae
Isolated from Patients with Gonorrhea Involving Two or More Sites
Authors: Catlin B. Wesley , Pace Paul J.
Published: June 2012

A system of auxotyping described in 1973 is based on the differing nutritional requirement patterns of
Neisseria gonorrhoeae
strains. Our ongoing evaluation of the reliability of auxotyping has involved a study of the constancy of characteristics of gonococci isolated at one time from two or more sites of a given subject. The auxotypes and minimal inhibitory concentration (MIC) of penicillin G were determined for 181 isolates obtained from 84 patients with uncomplicated gonorrhea, for 16 isolates from 8 couples with uncomplicated gonorrhea, and for 21 isolates from 12 other patients, 9 with disseminated gonococcal infection and three consorts. The penicillin MIC served to distinguish between many members of auxotypes 1, 2, and 3, which are commonly involved in uncomplicated gonorrhea. Thus, for proline-requiring gonococci (auxotype 2) the MIC ranged from 0.01 to 1.2 IU of penicillin per ml. The profile of gonococcal responses to seven other antibacterial drugs provided useful additional information where the extent of phenotypic similarity was in doubt. In all but seven instances, the gonococci isolated from different sites of the same patient, or from a consort, had the same nutritional requirements and penicillin MIC. The gonococci isolated from one patient with disseminated gonococcal infection and from one of her two sexual contacts had nutritional requirements for arginine, hypoxanthine, uracil, and thiamine pyrophosphate, whereas the strain isolated from her second contact differed in having no requirement for thiamine pyrophosphate. The paired cervical and rectal isolates from one patient with uncomplicated gonorrhea differed only with respect to a requirement for hypoxanthine. Pairs of isolates from three patients differed slightly in degree of susceptibility to penicillin. In the remaining two instances, however, numerous differences between the isolates from the endocervix and the anal canal of a given patient indicated the presence of concomitant infections with different strains of
N. gonorrhoeae
.
Rosamicin in Urethral and Vaginal Secretions and Tissues in Dogs and Rats
Authors: Hoyme Udo , Baumueller Axel , Madsen P. O.
Published: June 2012

In animal studies we investigated the distribution of rosamicin in plasma and urethral and vaginal tissues in rats as well as in urethral and vaginal secretions in dogs. We found concentration ratios between urethral secretion and plasma of 1.9 and between vaginal secretion and plasma of 2.4. The rosamicin concentrations in urethral and vaginal tissue significantly exceeded the levels of all other tissues investigated. Because rosamicin could be valuable for the treatment of bacterial urethritis and the colonization of the vaginal introitus with fecal bacteria in women, it should be investigated clinically in this respect.