bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Actinomycins Formed by Biosynthetic Incorporation of
cis
- and
trans
-4-Methylproline
Authors: Katz E. , Williams W. K. , Mason K. T. , Mauger A. B.
Published: June 2012

Streptomyces parvulus
(
Streptomyces parvullus
) normally produces actinomycin D; in the presence of
cis
-4-methylproline, this species synthesizes two additional actinomycins, designated K
1c
and K
2c
, in which one and two proline sites, respectively, are occupied by
cis
-4-methylproline. Analogously, actinomycins K
1t
and K
2t
are formed in the presence of
trans
-4-methylproline. Both mixtures were separated chromatographically, and the four novel actinomycins were obtained in crystalline form. Their biological activities were compared with that of actinomycin D in respect to inhibition of ribonucleic acid, deoxyribonucleic acid, and protein synthesis and antimicrobial potency. In all cases examined, the order of activity D > K
1t
> K
1c
> K
2t
> K
2c
was observed, and the same sequence prevailed in a spectroscopic measure of their binding to deoxyribonucleic acid. In addition, proton nuclear magnetic resonance studies revealed that the replacement of proline by
cis
-4-methylproline alters the conformation of the antibiotic molecule.
In Vitro Antibiotic Susceptibility of Salmonellae
Authors: Barros Facelucia , Korzeniowski Oksana M. , Sande Merle A. , Martins Katia , Santos Luiz Carlos , Rocha Heonir
Published: June 2012

In vitro antibiotic susceptibilities were determined for 101 strains of salmonellae. Resistance to chloramphenicol and ampicillin was low. Cefamandole was active against the majority of strains and deserves further evaluation.
Synergy Between Ticarcillin and Tobramycin Against
Pseudomonas aeruginosa
and
Enterobacteriaceae
In Vitro and In Vivo
Authors: Comber K. R. , Basker M. J. , Osborne Christine D. , Sutherland R.
Published: June 2012

The antibacterial activities of ticarcillin, carbenicillin, tobramycin, and gentamicin and of combinations of these antibiotics were measured against
Pseudomonas aeruginosa
and other gram-negative bacilli in vitro and in experimental mouse infections. Synergistic effects were produced by the penicillin/aminoglycoside combinations in growth inhibition tests and in bactericidal tests against many of the bacteria tested. Combinations of ticarcillin + tobramycin were more active in vitro than carbenicillin + gentamicin against
P. aeruginosa
but were no more active than the latter against other gram-negative bacilli. Ticarcillin + tobramycin and carbenicillin + gentamicin also demonstrated synergistic activities against
P. aeruginosa, Escherichia coli
, and
Enterobacter cloacae
in experimental mouse infection models. Thus, the penicillin/aminoglycoside combinations produced greater protective effects than the individual antibiotics against lethal intraperitoneal infections and also were more effective in reducing kidney counts of viable bacteria and kidney abscess formation in experimental pyelonephritis infections. As was the case in vitro, ticarcillin + tobramycin was more effective than carbenicillin + gentamicin against the experimental
P. aeruginosa
infections. The results of these in vitro and in vivo studies suggest that combined therapy with ticarcillin and tobramycin may be warranted in the treatment of serious infections due to
P. aeruginosa
and
Enterobacteriaceae
.
Novel R-Plasmid-Mediated Beta-Lactamase from
Klebsiella aerogenes
Authors: Petrocheilou V. , Sykes R. B. , Richmond M. H.
Published: June 2012

A novel β-lactamase with a broad spectrum of activity against penicillins and cephalosporins has been detected in a strain of
Klebsiella aerogenes
. Its synthesis is mediated by an R-plasmid of molecular weight 64 × 10
6
.
Antagonistic Action of Lipid Components of Membranes from
Candida albicans
and Various Other Lipids on Two Imidazole Antimycotics, Clotrimazole and Miconazole
Authors: Yamaguchi Hideyo
Published: June 2012

The growth-inhibitory activity of two imidazole antimycotics, clotrimazole and miconazole, against
Candida albicans
was significantly reversed when lipid extracts from protoplast membranes of the same organism were added to the assay medium together with the drugs. Of four major classes of lipids further separated from them, viz., phospholipids, triglycerides, sterol esters, and free sterols, the former two were capable of counteracting both drugs, whereas the latter two were not. However, even with phospholipids or triglycerides, no antagonism was noted when they were saturated by catalytic hydrogenation before use. The antagonistic effect of varying classes of commercial lipids, including phospholipids, acylglycerides, sterols, and fatty acids, was also studied by means of the agar diffusion technique. Significant antagonism to both drugs was observed with: (i) phospholipids with an unsaturated acyl group; (ii) acylglycerides, the ester portion of which consists of unsaturated fatty acid; (iii) ultraviolet-activated sterols; and (iv) unsaturated fatty acids of
cis
-configuration. By contrast, none of the saturated phospholipids and acylglycerides nor sterols was effective as an antagonist. With the exception only of lauric acid, all of a series of saturated fatty acids and unsaturated
trans
-fatty acids ranging from C
8
to C
18
in chain length were either minimally effective or completely ineffective. Essentially, there was no qualitative difference between clotrimazole and miconazole in the response to these various lipids.
Metabolic Fate of [
14
C]Cefamandole, a Parenteral Cephalosporin Antibiotic, in Rats and Dogs
Authors: Sullivan H. R. , Due S. L. , Kau D. L. K. , Quay J. F. , Miller W. M.
Published: June 2012

The biotransformation of the parenterally effective cephalosporin antibiotic cefamandole nafate (I) has been studied in rats and dogs. After rapid in vivo hydrolysis of the nafate pharmaceutical form to cefamandole (II), the antibiotic was found to be very resistant to metabolic degradation in both species. In dogs, cefamandole escaped metabolism and was eliminated as unaltered antibiotic almost exclusively by renal excretion. In rats, cefamandole was somewhat labile to metabolism; however, a major portion of the administered antibiotic was eliminated unchanged principally by renal excretion.
Mutagenic Studies of Folic Acid Antagonists
Authors: Genther C. S. , Schoeny R. S. , Loper J. C. , Smith C. C.
Published: June 2012

Compounds that compete with folic acid (folic acid antagonists [FAAs]) become limited in their usefulness in the treatment of leukemia, malaria, and bacterial infections by the rapid development of resistance. Assays of the plasma levels of certain of these FAAs led to the observation, in about 25% of the determinations, that a higher density of growth of
Streptococcus faecium
var.
durans
(ATCC 8043) was obtained at an FAA concentration just below the completely inhibitory level than at one-half this concentration. This and other considerations suggested that FAAs may act not only as selective agents for resistant organisms but also as mutagens. Seven FAAs including amethopterin, pyrimethamine, trimethoprim, chlorguanide triazine, an experimental quinazoline, WR-158,122, and two experimental triazines, WR-99,210 and WR-38,839, were tested for mutagenicity in the
Salmonella
reversion assay developed by Ames et al. (1975). All were found to be negative for strains TA1535, TA1537, TA1538, TA98, and TA100, both with and without microsomal activation. These compounds were then tested as mutagens for three traits in the folic acid-requiring
S. faecium
. FAAs were shown to cause mutations to folic acid independence, rifampin resistance, and FAA resistance. It is postulated that the FAAs induce mutations by causing thymine deprivation in the folic acid-requiring host.
Comparative Ototoxicity of Amikacin and Gentamicin in Cats
Authors: Christensen E. F. , Reiffenstein J. C. , Madissoo H.
Published: June 2012

The ototoxic potentials of two aminoglycoside antibiotics, amikacin and gentamicin, were compared in cats, using several otoxicity assessment techniques. Daily subcutaneous doses of 90 and 45 mg of amikacin per kg and 18 and 9 mg of gentamicin per kg (approximately six and three times the daily human dose) were administered to cats for extended periods of time until cochlear or vestibular dysfunction developed. Renal tissue damage and serum and perilymph antibiotic concentrations were also monitored. Amikacin selectively produced an impairment of cochlear function after an approximate cumulative dose of 3,600 mg/kg obtained after 41 days at 90 mg/kg per day or 78 days at 45 mg/kg per day, as determined by electrophysiological assessment. Gentamicin caused an impairment of vestibular function after an approximate cumulative dose of 700 mg/kg obtained after 42 days at 18 mg/kg per day or 68 days at 9 mg/kg per day, as determined by ataxia and impaired righting reflex. Gentamicin also moderately reduced electrophysiological cochlear responses and appeared to cause histological renal tissue change more frequently than did amikacin.
Neutrophil Toxicity of Amphotericin B
Authors: Chunn C. John , Starr P. R. , Gilbert David N.
Published: June 2012

The toxicity of amphotericin B (AmB) for neutrophils and the protective effect of serum cholesterol were investigated. Neutrophils were exposed in vitro to varying concentrations of AmB. As judged by trypan blue exclusion, neutrophil viability decreased by 40% (
P
< 0.001) within 30 min of incubation in sterol-free buffer containing 5 μg of AmB per ml. In the presence of 4 mg of cholesterol per 100 ml in buffer, the AmB concentration could be increased to 50 μg/ml before significant (
P
< 0.01) neutrophil toxicity occurred. Hexose monophosphate shunt activity of neutrophils incubated in serum or cholesterol-containing buffer with 10 μg of AmB per ml was normal. These results suggest that serum contains a protective factor, probably cholesterol, which protects neutrophils in vitro from the toxic effects of AmB.
Activity of Netilmicin Compared with Those of Gentamicin and Tobramycin Against Enterobacteria and
Pseudomonas aeruginosa
Authors: Chadwick Paul , Salmon Sheila , Taylor Beverley
Published: June 2012

The inhibitory activity of netilmicin against 500 isolates of gram-negative bacteria was compared with those of gentamicin and tobramycin. Netilmicin was considerably less active than tobramycin and slightly less inhibitory than gentamicin for
Pseudomonas aeruginosa
but was at least as active against
Escherichia coli
and
Klebsiella pneumoniae
as were the other two antibiotics. A few
Klebsiella
and
Serratia
isolates resistant to gentamicin and tobramycin were inhibited by netilmicin. All three antibiotics were strongly bactericidal for
E. coli, K. pneumoniae
and
P. aeruginosa
but had less lethal activity against the otherwise susceptible
Serratia
isolates tested. Some necessary precautions in reading minimal inhibitory concentrations on agar media are stressed, and some possible advantages of a 4-h bactericidal test, using a constant antibiotic concentration, are defined.
Conditional Killing Effect of Staphylococcin 1580 and Repair of Sublethal Injury in
Staphylococcus aureus
Authors: Weerkamp A. , Geerts W. , Vogels G. D.
Published: June 2012

Treatment of sensitive cells with staphylococcin 1580, a bacteriocin of
Staphylococcus epidermidis
, rapidly induced gross changes in the permeability of the membrane. However, only a small fraction of the cells was killed when treated cells were plated on media containing low amounts of salts. Killing was greatly enhanced by increasing the amounts of small cations incorporated in the plate medium and raising the alkalinity of the medium. The effect of cations correlated inversely with the ion radius. These conditions are shown to affect the repair mechanism of the sublethally injured cells rather than the interaction of staphylococcin 1580 with the cells. A model is proposed in which the killing effect of staphylococcin 1580 is a result of the inability of cells to maintain the protonmotive force at neutral or alkaline pH as a result of the permeation of cations. Recovery of sublethal damage appears to be a complex process requiring protein and probably also ribonucleic acid synthesis and the addition of a suitable energy source.
Synergistic Activity of Trimethoprim and Amikacin Against Gram-Negative Bacilli
Authors: Parsley Thomas L. , Provonchee Richard B. , Glicksman Caroline , Zinner Stephen H.
Published: June 2012

The in vitro effect of trimethoprim on the inhibitory and bactericidal activity of amikacin against 20 strains each of
Klebsiella pneumoniae
and
Serratia marcescens
, 15 strains of
Escherichia coli
, and 10 strains of
Pseudomonas aeruginosa
was examined by the checkerboard technique in microtiter plates. Trimethoprim had a synergistic effect on the inhibitory and bactericidal activity of amikacin against the majority of non-pseudomonas strains tested. The mean ± standard deviation fractional inhibitory concentration indexes were 0.59 ± 0.19 for the
Klebsiella
strains, 0.48 ± 0.18 for the
Serratia
strains, and 0.60 ± 0.22 for the
E. coli
strains tested. Respective mean ± standard deviation fractional bactericidal concentration indexes for these organisms were 0.55 ± 0.17, 0.54 ± 0.29, and 0.61 ± 0.22. A total of 40% of the
Klebsiella
strains, 80% of the
Serratia
strains, and 46% of the
E. coli
strains had a fractional inhibitory concentration equal to or less than 0.25 for both of these antimicrobial agents and were considered to be synergistically inhibited by the combination. By applying this criterion to bactericidal activity, synergy was demonstrated against 50, 65, and 46% of these strains, respectively. All of the
Enterobacteriaceae
tested were inhibited by clinically achievable concentrations of trimethoprim and amikacin. Antagonism was not demonstrated with any of the organisms tested. Trimethoprim had no antibacterial effect on the
Pseudomonas
strains and did not alter amikacin's activity against these bacteria.
Plasmids Carried by Antibiotic-Resistant Marine Bacteria
Authors: Sizemore Ronald K. , Colwell R. R.
Published: June 2012

Antibiotic-resistant bacteria were isolated from seawater samples collected in the Atlantic Ocean off the southeastern coast of the United States. Large numbers of antibiotic-resistant bacterial strains were found to be present in harbor and inshore waters; however, the percentage of resistant strains was higher for several seawater samples collected offshore than for those collected near shore. Bacteria resistant to tetracycline, chloramphenicol, and streptomycin were found in nearly all samples collected, including samples from 200 miles (about 522 km) offshore and at depths to 8,200 m. Sediment samples, in general, were found to contain smaller populations of resistant strains as compared with the seawater samples examined. Antibiotic-resistant bacteria exhibiting phenetic characteristics common to autochthonous marine bacterial species were examined in detail, and several of the isolates exhibited unstable antibiotic resistance, which was transferable to recipient
Escherichia coli
cells. Deoxyribonucleic acid preparations from 10 strains examined by ethidium bromide-cesium chloride density sedimentation revealed that 6 of the strains contained covalently closed circular plasmid deoxyribonucleic acid.
Identification of Drug Resistance Loci in Various Clinical Isolates of
Neisseria gonorrhoeae
Authors: Maier Thomas W. , Warner Patricia , Zubryzycki Leonard , Chila Maria
Published: June 2012

Extending previous results obtained for three strains of
Neisseria gonorrhoeae
, four naturally occurring, multiply resistant isolates were used in transformation studies. Six drug resistance loci corresponding to those found in the previously studied strains were identified. In addition, the
mtr
and
ery-2
loci were found to be allelic.
In Vitro Inhibition of Platelet Function and Coagulation by Pentamidine Isethionate
Authors: Kempin Sanford J. , Jackson Carl W. , Edwards Carol C.
Published: June 2012

Pentamidine isethionate is a trypanocidal drug used for the treatment of
Pneumocystis carinii
pneumonitis. Hematological complications have occasionally been reported and include anemia, leukopenia, and thrombocytopenia. We report here several qualitative abnormalities of in vitro platelet function and coagulation that have not been described previously. Platelets were exposed in vitro to concentrations of pentamidine isethionate ranging from 0.5 to 100 μg/ml of platelet-rich plasma. Clot retraction, platelet adhesiveness to glass beads, and platelet aggregation (adenosine 5′-diphosphate [ADP], thrombin, epinephrine, collagen, and ristocetin) were inhibited in a dose-dependent fashion. The addition of pentamidine isethionate after aggregation had been initiated with ADP reversed both primary and, to a lesser degree, secondary aggregation. Platelet factor 3 availability and serotonin uptake and release (using collagen as the releasing agent) were not inhibited. Serotonin release with 10
−4
M ADP was slightly inhibited. Pentamidine isethionate prolonged the thrombin time of plasma at concentrations of 5 μg/ml and greater. The prothrombin time was prolonged at concentrations greater than 10 μg/ml of plasma. The inhibition of aggregation was reversed by washing and resuspension in plasma or by the addition of calcium or magnesium ions.
Comparative Study of 6-Mercaptopurine Metabolism in Human Leukemic Leukocytes and L1210 Cells
Authors: Higuchi Tomihiko , Nakamura Toru , Uchino Haruto , Wakisaka Gyoichi
Published: June 2012

Leukocytes from patients with leukemia and L1210 cells from mice were examined for the rate of formation and cellular concentration of phosphoribosylpyrophosphate, the rate of thioinosinic acid formation, and a number of selected enzymes involved in purine nucleotide synthesis. The amount of thioinosinic acid formed in L1210 cells was much higher than that in human leukemic leukocytes. In cell extracts, the synthesis of thioinosinic acid was similar in both cell types, and the amount of purine phosphoribosyltransferase was not rate limiting in either case. Much higher concentrations and rates of formation of phosphoribosylpyrophosphate were found in L1210 cells than in human leukemic leukocytes. The difference in response to 6-mercaptopurine between L1210 cells and human leukemic leukocytes might be attributed to their difference in supply of phosphoribosylpyrophosphate. Phosphoribosylpyrophosphate-amidotransferase was found to be high in L1210 cells, but was not detected in human leukemic leukocytes.
Chartreusin: Production and Microbiological Assay
Authors: Hanka Ladislav J. , Gerpheide S. A.
Published: June 2012

Chartreusin was produced in the fermentation liquors of
Streptomyces chartreusis
at peak concentrations of 200 to 300 μg/ml. The titers could be increased by 200 to 300% or more by incorporating
d
-fucose, a part of the chartreusin molecule, into the fermentation media. A microbiological assay with
Sarcina lutea
could detect concentrations of the drug of 0.5 to 1.0 μg/ml.
Hepatotoxicity of Erythromycin Estolate During Pregnancy
Authors: McCormack William M. , George Harvey , Donner Alan , Kodgis Lorraine F. , Alpert Susan , Lowe Ernest W. , Kass Edward H.
Published: June 2012

Women in the second half of pregnancy, who were infected with genital mycoplasmas and who gave written informed consent, were randomly assigned to receive capsules of identical appearance containing erythromycin estolate, clindamycin hydrochloride, or a placebo for 6 weeks. Levels of serum glutamic oxalacetic transaminase (SGOT) were determined before and during treatment by a fluorometric method. All pretreatment levels of SGOT were normal (<41 units). Participants who received erythromycin estolate had significantly more abnormally elevated levels of SGOT (16/161, 9.9%) than did those who received clindamycin (4/168, 2.4%,
P
< 0.01) or those who received placebo (3/165, 1.8%,
P
< 0.01). Elevated levels of SGOT ranged from 44 to 130 U. Serum bilirubin levels were normal. Gamma-glutamyl transpeptidase activity was abnormal in six of six participants who had abnormal levels of SGOT while receiving erythromycin estolate. There were few associated symptoms, and all levels of SGOT returned to normal after cessation of treatment. The treatment of pregnant women with erythromycin estolate may be inadvisable.
Results of a Clinical Trial of Cefoxitin, a New Cephamycin Antibiotic
Authors: McCloskey Richard V.
Published: June 2012

Cefoxitin was administered intravenously to 143 patients, 67% of whom were seriously ill. The rate of cure or improvement was 93%. The study was conducted in two phases; the first was an open, controlled clinical comparison of cefoxitin and cephalothin. In this phase, 28 patients received cefoxitin and 29 received cephalothin. In the second phase, cefoxitin alone was used for the treatment of an additional 115 patients. Twenty bacteremic patients treated with cefoxitin were cured or improved in 95% of cases. The infecting organism was eradicated in all bacteremic patients. All of 14 anaerobic or predominantly anaerobic infections were cured or improved. The infecting anaerobic organism was eliminated in 86% of the cases. Twenty-five patients infected by cephalothin-resistant, cefoxitin-susceptible gram-negative rods were cured. Three patients each with infective endocarditis and osteomyelitis were cured. The incidence of adverse experiences was: 1.4% drug eruption; 2% each asymptomatic serum transaminase elevation and leukopenia; and 2.5% asymptomatic eosinophilia. The incidence of severe thrombophlebitis was 5%. No permanent or serious adverse reactions were encountered. Although the numbers of patients in some categories were too small to permit statistical evaluation, I feel that cefoxitin may be a useful new antibiotic for treatment of infections caused by cehalothin-resistant bacteria and by anaerobic organisms.
High-Pressure Liquid Chromatographic Assay of Netilmicin in Plasma
Authors: Peng Geoffrey W. , Jackson George G. , Chiou Win L.
Published: June 2012

A high-pressure liquid chromatographic method for the quantitative determination of netilmicin in plasma was developed. The procedures involve acetonitrile protein precipitation, methylene chloride extraction, and dansylation to form the fluorescent dansyl derivative of netilmicin, which is extracted into ethyl acetate and chromatographed on a reverse-phase column with aqueous acetonitrile as the mobile phase. A good linear relationship between peak height measurements and netilmicin concentrations was found. This method is sensitive and reproducible; a netilmicin concentration as low as 0.5 μg/ml can be measured with only 0.1 ml of plasma sample. The results of assays of plasma or serum samples by this high-pressure liquid chromatographic method correlate well with those obtained by microbiological assays.
Deoxyribonucleic Acid Polymerase of Wild-Type and Phosphonoacetic Acid-Resistant Mutant of Herpes Simplex Virus
Authors: Fridlender Bertold , Chejanovsky Nor , Becker Yechiel
Published: June 2012

The phosphonacetic acid (PAA)-susceptible deoxyribonucleic acid (DNA) polymerase of herpes simplex virus type 1 was partially purified and isolated in sucrose gradients and on double-strand DNA cellulose columns. The DNA polymerase isolated from cells infected with the PAA-resistant mutant had the same molecular weight as the wild-type enzyme (140,000 to 149,000) but was consistently more resistant to PAA.
Effect of Clavulanic Acid on Anaerobic Bacteria Resistant to Beta-Lactam Antibiotics
Authors: Wüst Jürg , Wilkins Tracy D.
Published: June 2012

The minimum inhibitory concentrations of penicillin and cephalothin necessary to inhibit growth of most anaerobic bacteria were reduced to a susceptible level by 1 to 5 μg of clavulanic acid per ml. In most cases, minimum inhibitory concentrations of cefoxitin were not affected.
PC-904, a New Semisynthetic Penicillin
Authors: Bodey Gerald P. , Weaver Suzanne , Pan Theresa
Published: June 2012

Sodium 6{
d
(−)-α(4-hydroxyl-1,5 naphthyridine-3-carboxamido)phenylacetamido} penicillanate (PC-904) is a new semisynthetic penicillin with broad-spectrum activity against gram-positive cocci and gram-negative bacilli. At a concentration of 1.56 μg/ml, it inhibited 100% of isolates of
Proteus mirabilis
, 89% of
Pseudomonas aeruginosa
, 67% of
Escherichia coli
, and 45% of
Enterobacter
spp. At a concentration of 12.5 μg/ml, it inhibited 75% of
Klebsiella
spp. and 67% of
Serratia marcescens
. PC-904 failed to inhibit the growth of gram-negative bacilli when large inocula were used. Some differences were noted when organisms were tested in different media or at different hydrogen ion concentrations. It is more active than mezlocillin, azlocillin, ticarcillin, carbenicillin, and amoxicillin against
E. coli, Klebsiella
spp., and
P. aeruginosa
.
Sensitive Bioassay for Vancomycin
Authors: Walker Cynthia A. , Kopp Bethel
Published: June 2012

An accurate and sensitive assay for vancomycin in serum and body fluids has not been available. This paper reports an assay for vancomycin that can detect serum and fluid levels as low as 0.8 μg/ml. A disk diffusion technique was designed employing buffered glucose minimal salts agar and
Bacillus subtilis
as an indicator strain. A linear relationship was obtained between zone diameter and concentration for vancomycin standards from 0.8 to 50 μg/ml prepared in pooled human serum. Results were accurate (<10% error) and reproducible (within-sample standard deviation, 0.25 μg/ml) for concentrations of from 0.8 to 25 μg of vancomycin per ml. Zone diameters were at least 6 mm larger on minimal salts agar than on standard assay media. The increased sensitivity and accuracy of the assay make it possible to accurately measure levels in cerebrospinal fluid and dialyzate fluid as well as in serum.
Stability and Blood Level Determinations of Cefaclor, a New Oral Cephalosporin Antibiotic
Authors: Foglesong M. A. , Lamb J. W. , Dietz J. V.
Published: June 2012

Cefaclor solutions in pH 2.5 and 4.5 buffers contained at least 90% of their initial activity after 72 h at 4°C. Samples in pH 6.0, 7.0, and 8.0 buffers contained 70, 46, and 34%, respectively, of their initial activity after 72 h at 4°C. After 72 h at 25°C, samples prepared with pH 2.5, 4.5, 6.0, 7.0, and 8.0 buffers contained 95, 69, 16, 5, and 3%, respectively, of their initial activity. After 72 h at 37°C, cefaclor solutions in pH 2.5 buffer contained 80% of the initial activity, whereas samples prepared in pH 4.5, 6.0, 7.0, and 8.0 buffers contained less than 20%. Laboratory-prepared plasma and serum samples showed an 8% loss in activity when incubated for 6 h at 4°C, a 51% loss when incubated for 6 h at 25°C, and a 48% loss when incubated for 2 h at 37°C. Clinical samples demonstrated a similar stability pattern. Degradation rates for cefaclor in commercially prepared serum increased from 4- to 10-fold in comparison to rates obtained when samples were made in human serum freshly prepared in our laboratory. Consequently, serum standards should be made in freshly prepared human serum.
Inhibition of Herpesvirus Replication and Herpesvirus-Induced Deoxyribonucleic Acid Polymerase by Phosphonoformate
Authors: Reno John M. , Lee Lucy F. , Boezi John A.
Published: June 2012

Phosphonoformate was found to be an inhibitor of the deoxyribonucleic acid polymerase induced by the herpesvirus of turkeys. The apparent inhibition constants were 1 to 3 μM. Phosphonoformate was also able to block the replication in cell culture of Marek's disease herpesvirus, the herpesvirus of turkeys, and herpes simplex virus. It was as effective as phosphonoacetate. Phosphonoformate was not an effective inhibitor of a phosphonoacetate-resistant mutant of the herpesvirus of turkeys nor of its induced deoxyribonucleic acid polymerase.
Susceptibility of
Escherichia coli
to Bactericidal Action of Lactoperoxidase, Peroxide, and Iodide or Thiocyanate
Authors: Thomas Edwin L. , Aune Thomas M.
Published: June 2012

The bactericidal action that results from lactoperoxidase-catalyzed oxidation of iodide or thiocyanate was studied, using
Escherichia coli
as the test organism. The susceptibility of intact cells to bactericidal action was compared with that of cells with altered cell envelopes. Exposure to ethylenediaminetetraacetic acid, to lysozyme and ethylenediaminetetraacetic acid, or to osmotic shock were used to alter the cell envelope. Bactericidal action was greatly increased when the cells were exposed to the lactoperoxidase-peroxide-iodide system at low temperatures, low cell density, or after alteration of the cell envelope. When thiocyanate was substituted for iodide, bactericidal activity was observed only at low cell density or after osmotic shock. Low temperature and low cell density lowered the rate of destruction of peroxide by the bacteria. Therefore, competition for peroxide between the bacteria and lactoperoxidase may influence the extent of bactericidal action. Alteration of the cell envelope had only a small effect on the rate of destruction of peroxide. Instead, the increased susceptibility of these altered cells suggested that bactericidal action required permeation of a reagent through the cell envelope. In addition to altering the cell envelope, these procedures partly depleted cells of oxidizable substrates and sulfhydryl components. Adding an oxidizable substrate did not decrease the susceptibility of the altered cells. On the other hand, mild reducing agents such as sulfhydryl compounds did partly reverse bactericidal action when added after exposure of cells to the peroxidase systems. These studies indicate that alteration of the metabolism, structure, or composition of bacterial cells can greatly increase their susceptibility to peroxidase bactericidal action.
Acidometric Agar Plate Method for Ampicillin Susceptibility Testing of
Haemophilus influenzae
Authors: Park Choong H. , Lopez Jill S. , Cook C. Barrie
Published: June 2012

The need for an accurate and rapid method of testing ampicillin susceptibility of
Haemophilus influenzae
, especially strains isolated from patients with meningitis and septicemia, is indisputable. Various methods have been employed for this purpose. Each has advantages and disadvantages. This report describes a modification of the capillary acidometric procedure in which an agar plate is substituted for a tube. All beta-lactamase results obtained by this modified technique correlated with minimal inhibitory concentrations determined in liquid media and the chromogenic cephalosporin substrate method. This modified acidometric agar procedure is a simple, inexpensive, accurate, and rapid way to determine
H. influenzae
susceptibility to ampicillin.
Modified agar dilution method for rapid antibiotic susceptibility testing of anaerobic bacteria
Authors: Hanson C W , Martin W J
Published: June 2012

A simplified method has been developed for agar dilution antimicrobial susceptibility testing of anaerobic bacteria, designed to economize on time and money when only a few isolates need to be tested. The procedure is based on the principle of using filter paper disks as carriers of the antibiotic and 35- by 10-mm petri dishes which, when inoculated with the Steers replicator, can test up to four organisms per plate. The procedure was run in parallel with conventional agar dilution techniques and showed 95% agreement to within one dilution for all minimal inhibitory concentrations recorded on fresh anaerobic isolates from clinical specimens. The technique was further simplified by using commercially available antibiotic-containing disks, thereby alleviating the tedious and time-consuming procedure of preparing the disks. The data indicated that 48- to 72-h diffusion periods were sufficient to achieve a uniform concentration of the antibiotic in the petri plate and that the antibiotics were stable at room temperature for that period of time. In terms of applicability and relevance to the needs of the clinical microbiology laboratory, the modified agar dilution method for rapid antimicrobial susceptibility testing of individual anaerobic isolates was found to be superior to the broth dilution method since it was easier to read and required considerably less set up time.
Activity of flumequine against Escherichia coli: in vitro comparison with nalidixic and oxolinic acids
Authors: Greenwood D
Published: June 2012

The in vitro activity of the new antibacterial agent, flumequine, against Escherichia coli was compared with those of oxolinic acid and nalidixic acid. As judged by turbidimetric criteria, flumequine was considerably more active than nalidixic acid and slightly less active than oxolinic acid against both nalidixic acid-susceptible and -resistant strains. Resistance to all three drugs could be easily induced in vitro. The comparative efficacy of flumequine, oxolinic acid, and nalidixic acid was also tested in an in vitro model of the treatment of bacterial cystitis. In this system, suppression of bacterial growth was obtained with markedly lower concentrations of flumequine and oxolinic acid than of nalidixic acid, but prevention of the emergence of bacterial populations that exhibited increased resistance to these compounds depended on the maintenance of adequate drug levels.
Penicillin and netilmicin in treatment of experimental enterococcal endocarditis
Authors: Carrizosa J , Kaye D
Published: June 2012

Successful therapy of enterococcal endocarditis requires the use of a combination of penicillin plus an aminoglycoside. The effectiveness of penicillin (Pen), streptomycin (Str), and netilmicin (Net), a new aminoglycoside, alone and in combination, were studied in vitro and in the treatment of left-sided enterococcal endocarditis in rabbits. In vitro Pen+Str or Net resulted in a more rapid and more complete bactericidal effect than Pen, Str, or Net alone against a Str-susceptible strain of enterococcus (strain 1). Against a highly Str-resistant strain (strain 2), Pen+Net showed an advantage over Pen, Str, or Net alone, or Pen+Str. Endocarditis was produced in rabbits with strain 1 or 2, and treatment was initiated 24 h later. Rabbits were treated for 48 h or 5 days with procaine Pen, Pen+Str, or Pen+Net. With strain 1, numbers of enterococci in the vegetations decreased more rapidly with Pen+Str or Pen+Net treatment than with Pen, Str, or Net alone. With strain 2, Pen+Net showed a clear advantage over Pen, Str, Net, or Pen+Str. Net in combination with Pen showed synergistic in vitro activity and was more effective than Pen alone in the treatment of enterococcal endocarditis in rabbits caused by both Str-susceptible and Str-resistant strains.
Differential Binding of Penicillin by Membrane Fractions from Penicillin-Susceptible and -Resistant Gonococci
Authors: Rodriguez William J. , Saz Arthur K.
Published: June 2012

An inverse relationship between binding of [
14
C]penicillin to cells of
Neisseria gonorrhoeae
and the minimal inhibitory concentration of penicillin was recently reported by us. Herein we report a similar relationship in binding by cytoplasmic membranes derived from 10 strains of gonococci. Membranes were extracted after Braun homogenization and differential centrifugation of the resulting extracts. Membranes derived from penicillin-susceptible cells bound 140 to 200 nmol of [
14
C]penicillin per g of enzyme, whereas relatively nonsusceptible strains bound 18 to 59 nmol. Binding by cell walls was only a small fraction of the total binding and probably represents contamination of the walls by membrane. Pretreatment of cell membranes with either unlabeled penicillin or cephalothin prior to [
14
C]penicillin exposure markedly decreased
14
C binding. Slab gel electrophoresis of membranes revealed 13 protein bands, 8 of which were labeled.
Antimicrobial Susceptibility of
Haemophilus ducreyi
Authors: Hammond Gregory W. , Lian Chang Joo , Wilt John C. , Ronald Allan R.
Published: June 2012

The susceptibility of 19 isolates of
Haemophilus ducreyi
from a recent chancroid outbreak and four reference strains was determined in vitro to 13 antimicrobial agents. The rabbit intradermal test for virulence was positive for all of the local isolates, but not for the reference strains. The “nonvirulent” reference strains were inhibited by lower minimum inhibitory concentrations (MICs) of most agents tested. For the virulent isolates, the range of MICs (in micrograms per milliliter) of the following were: of vancomycin, 8 to 128; of polymyxin, 32 to 128; of cloxacillin, 32 to 64; of tetracycline, 0.5 to 32; of cephalothin, 4 to 8; of doxycycline, 0.25 to 8; and of kanamycin, 1 to 8. Three strains were resistant to penicillin and ampicillin (MIC ≥ 128 μg/ml), and these three strains produced β-lactamase. The remainder were susceptible to 4 μg/ml. All strains were susceptible to rifampin (MIC ≤ 1 μg/ml), chloramphenicol (MIC ≤ 4 μg/ml), sulfisoxazole (MIC ≤ 8 μg/ml), and nalidixic acid (MIC ≤ 8 μg/ml). These susceptibilities of
H. ducreyi
indicate several antimicrobial agents that may be effective for chancroid treatment and support the use of vancomycin in a selective medium for the culture of chancroid genital ulcers.
Plasmid-Determined Resistance to Boron and Chromium Compounds in
Pseudomonas aeruginosa
Authors: Summers Anne O. , Jacoby George A.
Published: June 2012

Plasmids determining resistance to arsenic, mercury, silver, and tellurium compounds in
Escherichia coli
and
Pseudomonas aeruginosa
were tested for resistance to 40 other metal compounds. Resistance to trivalent boron and hexavalent chromium compounds was a property of certain
P. aeruginosa
plasmids.
Beta-Lactamases: Determination of Their Isoelectric Points
Authors: Barthelemy Michel , Guionie Marlène , Labia Roger
Published: June 2012

Important discrepancies in isoelectric points (pI) of β-lactamases were observed depending on the experimental procedure used for their determination: isoelectric focusing (IEF) in sucrose density gradients or analytical IEF in thin-layer polyacrylamide gels (PA). The variations, negligable in the case of TEM-like β-lactamases, appeared to be important in the case of cephalosporinases and are related to an artifact which appears in PA-IEF. This has been clearly shown with β-lactamase preparations from the following bacterial strains:
Pseudomonas aeruginosa
NCTC 8203 (pI = 8.7),
P. aeruginosa
NCTC 10701 (pI = 9.4), and
Proteus morganii
NCTC 235 (pI = 8.3). The data previously obtained by PA-IEF were much lower.
Fungal Toxicity of Phosfon D and Its Reversion by Lipids
Authors: Vannini G. L. , Dall'olio G. , Donini A.
Published: June 2012

The growth retardant Phosfon D inhibits the growth of some yeasts and human pathogenic filamentous fungi. The toxic effects of the compound on the dermatophyte
Microsporum cookei
were completely reversed by adding ergosterol and oleic acid to the medium. The significance of these findings is discussed.
Susceptibility of Skin and Throat Strains of Group A Streptococci to Rosamicin and Erythromycin
Authors: Saroglou George , Bisno Alan L.
Published: June 2012

The minimal inhibitory concentrations of rosamicin and erythromycin were compared for 210 strains of group A streptococcus isolated from a diverse spectrum of streptococcal diseases. Of these strains, 97.6% were inhibited by 0.1 to 0.2 μg of rosamicin per ml, whereas 90.9% were inhibited by 0.025 to 0.05 μg of erythromycin per ml. The minimal inhibitory concentration of rosamicin for 154 strains exceeded that of erythromycin by at least fourfold. Five group A strains of streptococcus that were highly resistant to erythromycin were even more resistant to rosamicin.
Antibacterial Activity of Apalcillin (PC-904) Against Gram-Negative Bacilli, Especially Ampicillin-, Carbenicillin-, and Gentamicin-Resistant Clinical Isolates
Authors: Noguchi Hiroshi , Kubo Masako , Kurashige Satonori , Mitsuhashi Susumu
Published: June 2012

Apalcillin (PC-904) is active against carbenicillin- and ampicillin-resistant strains of gram-negative bacilli. Among
Pseudomonas aeruginosa
strains highly resistant to carbenicillin (≥3,200 μg/ml), half of them were susceptible to PC-904 at a concentration of 50 to 1,600 μg/ml. The minimal inhibitory concentration of PC-904 against
P. aeruginosa
strains resistant to carbenicillin (400 to 1,600 μg/ml) ranged from 3.1 to 25 μg/ml. Ampicillin- and carbenicillin-resistant
Enterobacteriaceae
strains were similarly susceptible to PC-904. However, drug resistance to PC-904 was already apparent among some strains of
P. aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, P. vulgaris
, and
P. morganii
, recently isolated in Japan; i.e., 4, 35, 32, 4, 6, and 14% of strains isolated were resistant. PC-904 was more active, on the other hand, than ampicillin and carbenicillin against antibiotic-susceptible
Enterobacteriaceae
and also showed high activity against most species of
Pseudomonadaceae
, especially
P. cepacia
and
P. aeruginosa
. The minimum inhibitory concentrations of PC-904 were greatly affected by inoculum size when the organisms tested were strains producing large amounts of beta-lactamase.
In Vitro Susceptibility of
Haemophilus influenzae
to Sulfamethoxazole-Trimethoprim and Cefaclor, Cephalexin, and Cephradine
Authors: Sinai R. , Hammerberg S. , Marks M. I. , Pai C. H.
Published: June 2012

Sulfamethoxazole-trimethoprim and three oral cephalosporins, cefaclor, cephalexin, and cephradine, were evaluated in vitro as possible alternatives to chloramphenicol in the treatment of non-central nervous system infections due to ampicillin-resistant
Haemophilus influenzae
. Sixty-four isolates of
H. influenzae,
including 31 β-lactamase-positive strains, were tested by the agar dilution method. All strains were inhibited by 0.78/0.039 μg sulfamethoxazole-trimethoprim per ml and by 0.78 μg of chloramphenicol per ml. At 6.25 μg/ml, 100, 11, and 3% of all strains were inhibited by cefaclor, cephalexin, and cephradine, respectively. Thus, on the basis of drug concentrations presumably achievable in serum, 100% of strains were susceptible to sulfamethoxazole-trimethoprim, chloramphenicol, and cefaclor. However, a considerable inoculum effect was noted with both β-lactamase-positive and -negative strains, when tested with sulfamethoxazole-trimethoprim; the minimal inhibitory concentrations of cefaclor were only slightly affected. Also, synergistic effects of sulfamethoxazole-trimethoprim, sulfamethoxazole-erythromycin, and sulfamethoxazole-cefaclor were seen when combinations were tested against both β-lactamase-positive and -negative strains, as determined by minimal inhibitory concentrations measured by the broth dilution method and by killing curve analyses. These results support further evaluation of these combinations and of cefaclor alone for the treatment of non-central nervous system infections due to
H. influenzae
.
Production and Property of Beta-Lactamases in
Streptomyces
: Comparison of the Strains Isolated Newly and Thirty Years Ago
Authors: Ogawara Hiroshi , Horikawa Susumu , Shimada-Miyoshi Sachiko , Yasuzawa Koji
Published: June 2012

Productivity and property of β-lactamases of
Streptomyces
strains isolated from soil some 30 years ago were studied in comparison with those of the newly isolated strains. At least three-quarters of the
Streptomyces
strains produced β-lactamase constitutively and extracellularly, mainly as penicillinases, as in the cases of those from the newly isolated strains. Strains such as
S. albus, S. diastatochromogenes, S. fradiae,
and
S. lavendulae
were the highest producing strains, and the amounts of β-lactamase activity they produced were comparable to those produced by
Bacillus cereus
569/H and
B. licheniformis
749/C. In isoelectric focusing, most strains contained one main β-lactamase band with a number of satellite bands, but some strains contained one band only. Although β-lactamases from most strains showed isoelectric points of pH 5 to 6, some strains produced β-lactamases with strongly basic isoelectric points of pH 8 to 9. Molecular weights were between 20,000 and 30,000. From these results, it is suggested that the proportion of the producing strains of
Streptomyces
and the properties of the β-lactamases have not been affected significantly by the introduction of penicillin into the natural environment, in contrast to the cases of other microorganisms.
Inhibition of Platelet Function by Sulbenicillin and Its Metabolite
Authors: Ikeda Yasuo , Kikuchi Masao , Matsuda Shigeyoshi , Toyama Keisuke , Hasegawa Mitsuto , Watanabe Kiyoaki , Ando Yasuhiko
Published: June 2012

The effect of sulbenicillin and its major metabolite, α-sulfobenzylpenicilloic acid, on platelet function was investigated. Sulbenicillin caused inhibition of platelet aggregation and release reaction in the same manner as carbenicillin. α-Sulfobenzylpenicilloic acid was found to cause much stronger inhibition of platelet function. The results indicate that the strong inhibitory action of α-sulfobenzylpenicilloic acid may also take part in impaired platelet functions following administration of sulbenicillin to humans.
Characterization of a Small Plasmid Determining Resistance to Erythromycin, Lincomycin, and Vernamycin B
α
in a Strain of
Streptococcus sanguis
Isolated from Dental Plaque
Authors: Yagi Yoshihiko , McLellan Thomas S. , Frez William A. , Clewell Don B.
Published: June 2012

A plasmid determining resistance to erythromycin (inducible), lincomycin, and vernamycin B
α
was isolated from a strain of
Streptococcus sanguis
isolated from dental plaque of a patient who had been on erythromycin therapy for an extended period of time. The plasmid, designated pAM77, had a molecular weight of 4.5 × 10
6
and was present to the extent of one to two copies per bacterial chromosome. The plasmid could transform
S. sanguis
strain Challis.
Oxidation of
Escherichia coli
Sulfhydryl Components by the Peroxidase-Hydrogen Peroxide-Iodide Antimicrobial System
Authors: Thomas Edwin L. , Aune Thomas M.
Published: June 2012

The chemical modification of bacterial components was studied following incubation of
Escherichia coli
with the peroxidase-hydrogen peroxide (H
2
O
2
)-iodide (I
−
) antimicrobial system or with iodine (I
2
). The oxidation of cell sulfhydryls and the iodination of cell components were measured. Both the peroxidase system and I
2
oxidized sulfhydryls. When the I
−
concentration in the peroxidase system was greater than 100 μM, the peroxidase system and I
2
were equivalent. That is, sulfhydryl oxidation or killing per mole of H
2
O
2
equaled that per mole of I
2
. These results were consistent with peroxidase-catalyzed oxidation of I
−
to yield 1 mol of I
2
per mol of H
2
O
2
. Sulfhydryls were oxidized to yield sulfenic acids and free I
−
. With I
−
concentrations in the range of 10 to 100 μM, the amount of sulfhydryls oxidized by the peroxidase system could exceed the amount of I
−
. Because the oxidation of sulfhydryls to sulfenic acids did not consume I
−
, one I
−
ion could participate in the oxidation of many sulfhydryls. With I
−
concentrations lower than 10 μM, complete oxidation of sulfhydryls was not obtained. Incorporation of I
−
into iodinated derivatives of bacterial components partly depleted the system of I
−
and limited the formation of I
2
. These results indicated that antimicrobial activity was due to peroxidase-catalyzed oxidation of I
−
to I
2
, followed by I
2
oxidation of cell components. There was a direct relationship between sulfhydryl oxidation and antimicrobial action. Although iodination of bacterial components accompanied sulfhydryl oxidation, the amount of I
−
incorporation was not directly related to antimicrobial action. Also, incorporation of I
−
interfered with antimicrobial action at low I
−
concentrations.
Susceptibility of Candida albicans to Miconazole
Authors: Bannatyne Robert M. , Cheung Rose
Published: June 2012

A total of 439 clinical isolates of
Candida albicans
were tested for susceptibility to miconazole by the agar dilution technique. When tests were read at 48 and 24 h, 56 and 84%, respectively, of the strains were completely inhibited by 4.0 μg of miconazole per ml, the estimated upper limit of probable clinical susceptibility.