bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Susceptibility of Anaerobic Bacteria to Minocycline, Doxycycline, and Tetracycline
Authors: Chow Anthony W. , Patten Valerie , Guze Lucien B.
Published: June 2012

The comparative susceptibility of 622 recent clinical isolates of anaerobic bacteria to minocycline, doxycycline, and tetracycline was determined by an agar-dilution technique. In addition to
Bacteroides fragilis
, a variety of other anaerobic bacteria was resistant to achievable blood concentrations of tetracycline (55% inhibited by 6.25 μg/ml) and doxycycline (58% inhibited by 2.5 μg/ml). In contrast, minocycline was significantly more active (
P
< 0.05) than both doxycycline and tetracycline, and 70% of strains were inhibited by achievable blood concentrations of this antibiotic (2.5 μg/ml). The enhanced activity of minocycline was particularly striking for
Peptococcus asaccharolyticus, P. magnus, P. prevotii, Peptostreptococcus anaerobius
, and
Bacteroides melaninogenicus
. Further evaluation of the clinical efficacy of minocycline against anaerobic infections is indicated.
Pseudomonas aeruginosa
R Factors Determining Gentamicin Plus Carbenicillin Resistance from Patients with Urinary Tract Colonizations
Authors: Korfhagen Thomas R. , Loper John C. , Ferrel James A.
Published: June 2012

R factors determining multiple resistance including both gentamicin and carbenicillin have been identified in high incidence among hospital isolates of
Pseudomonas aeruginosa
. The factors are readily transmitted to other
P. aeruginosa
but not to
Escherichia coli
strains K-12 or C, or to
Proteus mirabilis
. R factor-containing isolates are predominantly immunotype 7 isolated from urinary sources.
RPL11, an R Factor of
Pseudomonas aeruginosa
Determining Carbenicillin and Gentamicin Resistance
Authors: Korfhagen T. R. , Loper J. C.
Published: June 2012

R factor RPL11 from
Pseudomonas aeruginosa
determines multiple drug resistance including resistance to gentamicin and carbenicillin. The host range and incompatibility properties of RPL11 are those of incompatibility group P-2. Strains harboring the factor are not altered with respect to the major immunotypes 1 through 7 of Parke-Davis, or with respect to pyocin type by using the 18 indicators of Jones and co-workers. Analytical ultracentrifugation of crude extracts of R factor-containing strains shows a band of satellite DNA with a buoyant density of 1.717 g/cm
3
.
Relationship Between Polyene Resistance and Sterol Compositions in
Cryptococcus Neoformans
Authors: Kim S. J. , Kwon-Chung K. J. , Milne G. W. A. , Hill W. B. , Patterson G.
Published: June 2012

Six mutants of
Cryptococcus neoformans
resistant to nystatin and pimaricin and three mutants resistant to amphotericin B were isolated by ultraviolet irradiation techniques from two wild-type strains. The major sterols of the wild-type strains were Δ
7
-ergosten-3β-ol and ergosterol. All six mutants resistant to nystatin and pimaricin showed either loss of ergosterol and concurrent production of Δ
7, 22
-ergostadien-3β-ol and Δ
7
-ergosten-3β-ol, or loss of both the wild-type sterols, with production of Δ
8(9)
-ergosten-3β-ol and Δ
5, 8(9), 22
-ergostatrien-3β-ol. The mutants producing Δ
7, 22
-ergostadien-3β-ol and Δ
7
-ergosten-3β-ol showed relatively low levels of resistance to nystatin and pimaricin, whereas the mutants producing Δ
8(9)
-ergosten-3β-ol and Δ
5, 8(0), 22
-ergostatrien-3β-ol showed a high level of resistance to either drug. Although highly resistant to amphotericin B, however, the three mutants produced sterol compositions identical to those of the wild types, indicating that the strains acquired resistance other than by alteration of the membrane sterols. The mutants producing Δ
8(9)
and Δ
5, 8(9), 22
sterols were not virulent for mice, showed reduced growth rates at 25 C, and failed to grow at 37 C. The other mutants showed a slightly reduced rate of growth both at 25 and 37 C, and the virulence in mice was slightly reduced in comparison with that of the wild types. These comparisons were on gross observations and were not statistically analyzed.
Production and Mode of Action of Lactocin 27: Bacteriocin from a Homofermentative
Lactobacillus
Authors: Upreti G. C. , Hinsdill R. D.
Published: June 2012

Lactobacillus helveticus
strain LP27 produced a bacteriocin, lactocin 27, in dialyzable and nondialyzable forms. No evidence was obtained to indicate that lactocin 27 was under the control of extrachromosomal plasmids. Lactocin 27 had a bacteriostatic effect on the indicator,
Lactobacillus helveticus
strain LS18. It inhibited primarily protein synthesis without affecting deoxyribonucleic acid and ribonucleic acid synthesis or adenosine 5′-triphosphate levels. Treatment of susceptible cells with the lactocin did not cause leakage of ultraviolet-absorbing material, but caused the efflux of potassium ions and the influx of sodium ions. It adsorbed non-specifically to various bacterial species irrespective of their susceptibility to lactocin 27. However, the presence of specific receptors has not been ruled out.
Varicella-Zoster Virus and Subcutaneous Cytarabine: Correlation of In Vitro Sensitivities to Blood Levels
Authors: Zaky Dawlat A. , Betts Robert F. , Douglas R. Gordon , Bengali Kathleen , Neil Gary L.
Published: June 2012

The susceptibility of 26 strains of varicella-zoster virus to cytarabine was tested in vitro by measuring reduction in number and size of plaques using human foreskin fibroblast cells. Most strains showed 50% reduction of plaque number by 0.125 μg of cytarabine per ml or less. Cytarabine levels in sera of 12 patients after a single subcutaneous injection of 50 mg/M
2
exceeded this inhibitory level for a period of 75 min. Thus, the subcutaneous route is a potentially useful method of administration of cytarabine for antiviral drug trials.
Binding of Aminoglycoside Antibiotics to Filtration Materials
Authors: Wagman Gerald H. , Bailey Janet V. , Weinstein Marvin J.
Published: June 2012

An investigation to study adsorption of gentamicin and other related aminoglycoside antibiotics to cellulose, diatomaceous earth (Celite), and Seitz filter sheets was carried out. Experiments with five aminoglycosides indicated that 30 to 100% of these antibiotics was adsorbed to cellulose depending on the ratio of antibiotic to adsorbent, and the total quantity could not be removed by acidification. Similarly, a study with gentamicin found adsorption to diatomaceous earth to be in the range of 33 to 98%. Neomycin and gentamicin were also readily adsorbed to Seitz filter sheets. The data indicate that large losses may occur during filtration of these antibiotics under certain conditions, and care should be taken to properly evaluate results during studies with these compounds in the presence of adsorbent materials.
BL-P1654, Ticarcillin, and Carbenicillin: In Vitro Comparison Alone and in Combination with Gentamicin Against
Pseudomonas aeruginosa
Authors: Wald Ellen R. , Standiford Harold C. , Tatem Beverly A. , Calia Frank M. , Hornick Richard B.
Published: June 2012

Minimum inhibitory concentrations of carbenicillin, ticarcillin, and BL-P1654 were determined for 89 clinical isolates of
Pseudomonas aeruginosa
. Ticarcillin was generally twice as active and BL-P1654 eight to 16 times as active as carbenicillin. Usually carbenicillin and ticarcillin killed at the same concentration or twice the concentration needed to inhibit, whereas 400 μg of BL-P1654 per ml was not bactericidal for the majority of isolates tested. The inhibitory effect of all three drugs varied markedly with the size of bacterial inoculum. When therapeutically achievable concentrations were used, adding gentamicin enhanced the inhibitory and bactericidal activity of all three penicillin derivatives for the majority of isolates. However, inhibition of isolates highly resistant to gentamicin was not improved by combining the semisynthetic penicillins with gentamicin.
Inhibitory Effects of Lipophilic Acids and Related Compounds on Bacteria and Mammalian Cells
Authors: Sheu C. W. , Salomon D. , Simmons J. L. , Sreevalsan T. , Freese E.
Published: June 2012

The inhibitory effect of lipophilic acids, antimicrobial food additives, and analgesics-antipyretics was examined at concentrations from 0.1 to 100 mM in bacteria (
Bacillus subtilis
and
Escherichia coli
) and mammalian cells (HeLa, human fibroblasts, and mouse neuroblastoma cells). Most compounds inhibit the growth of HeLa cells about as efficiently as that of
B. subtilis
. However, butyrate and propionate, as well as acetaminophen, antipyrene, phenacetin, and salicylamide, inhibit HeLa at millimolar concentrations whereas, at least 10 times higher concentrations are needed to inhibit
B. subtilis
. The concentrations needed to inhibit growth by 50% decrease with increasing octanol-water partition coefficients of the compound. Growth of
E. coli
is inhibited similar to that of
B. subtilis
by all compounds except butylbenzoate, decanoate, and linoleate which cannot penetrate the lipopolysaccharide layer. All growth inhibitors inhibit amino acid uptake into bacteria and their vesicles, and oxygen consumption in bacteria. In HeLa cells or human fibroblasts, neither amino acid uptake nor adenine 5′-triphosphate synthesis are inhibited by fatty acids at concentrations that completely inhibit growth. Short chain fatty acids (propionate, butyrate, and pentanoate) induce in HeLa the formation of cell processes. In neuroblastoma cells, grown in the presence of 10% fetal calf serum, butyrate also induces such processes which slowly continue to grow in length for at least 7 days; these processes differ in speed of formation, width, and cycloheximide susceptibility from the thin processes produced by serum deprivation alone.
Desferrioxamine B, an Inhibitor of
Escherichia coli
Motility, Reversing the Stimulating Effect of Cyclic Adenosine 3′,5′-Monophosphate
Authors: Maruyama Hiromi B. , Azuma Haruyoshi , Kotoh Yoshiaki , Suhara Yasuji
Published: June 2012

A substance inhibiting
Escherichia coli
motility was isolated by “motilometry” assay from the culture broth of
Streptomyces
sp. strain NR9GG8 and was found to be identical with desferrioxamine B. Its inhibitory effect was reversed by cyclic adenosine 3′,5′-monophosphate (cAMP), while the motility stimulation by cAMP was diminished by this inhibitor. Its effects on various enzymes involved in cAMP metabolism of function of cAMP were examined.
Comparative Efficacy of Cephalexin and Ampicillin for Shigellosis and Other Types of Acute Diarrhea in Infants and Children
Authors: Nelson John D. , Haltalin Kenneth C.
Published: June 2012

Most ampicillin-resistant
Shigella
are susceptible to cephalexin. Randomized treatment with cephalexin or ampicillin was given to 154 infants and children with acute diarrhea. Rectal swab cultures revealed
Shigella
in 42%,
Salmonella
in 6%, enteropathogenic
Escherichia coli
in 2%, and no pathogen in 50%. Cephalexin failed to eradicate
Shigella
after 5 days of treatment in 76% of patients as contrasted with 28% of ampicillin-treated patients with susceptible organisms.
Shigella
persisted in 78% of ampicillin-treated patients with resistant organisms. Diarrhea lasted more than 5 days in 43% of cephalexin-treated patients, in 56% of the ampicillin group with resistant organisms, but in only 9% of ampicillin-treated patients with susceptible organisms. The failure of cephalexin was due to the relatively high minimal inhibitory concentrations and minimal bacterial concentrations of 5 or 10 μg/ml and, although serum concentrations were twice the minimal bacterial concentration, they were not sufficient to demonstrate killing by the serum dilution method. In vitro susceptibility or resistance of
Shigella
to ampicillin correlated with clinical success or failure. Cephalexin is not a suitable drug for treatment of shigellosis in patients with ampicillin-resistant organisms.
Effects of Minocycline and Other Antibiotics on
Fusobacterium necrophorum
Infections in Mice
Authors: Kuck Nydia A.
Published: June 2012

Several antibiotics were evaluated in model infections produced in mice with each of two strains of
Fusobacterium necrophorum
. In one model, local abscesses occurred at the site of subcutaneous injection; in another intra-abdominal abscesses were produced when the organisms were injected into the peritoneal cavity. Treatment with effective antibiotics prevented the formation of abscesses or minimized the size of the lesions. Several treatment schedules were used. Minocycline was the most active antibiotic of the seven agents tested against both strains and in both models. Clindamycin was equal to minocycline against one strain with certain multiple dose treatment schedules and less active with others. Protective effects in mice were achieved with serum levels of minocycline and clindamycin that appear to be clinically achievable. Doxycycline was less active than minocycline, and tetracycline was relatively ineffective, as were cephalexin, ampicillin and penicillin G.
Interactions of Carbenicillin and Ticarcillin with Gentamicin
Authors: Davies Michael , Morgan John R. , Anand Chanda
Published: June 2012

The in vitro inactivation of gentamicin by carbenicillin and a new semisynthetic penicillin, ticarcillin (BRL 2288), has been demonstrated. Gentamicin half-lives have been studied in eight patients with end-stage renal failure, and a 25 to 74% reduction in half-life has resulted from the concomitant administration of therapeutic doses of carbenicillin and ticarcillin.
Effect of Tilorone Treatment on Intracellular Microbial Infections in Specific-Pathogen-Free Mice
Authors: Collins Frank M.
Published: June 2012

Specific-pathogen-free CD-1 mice were treated orally with the drug tilorone (2,7-bis[2-diethylaminoethoxy]fluoren-9-one hydrochloride) at dosages of 10 or 100 mg per kg of body weight. Drug was given 24 h before challenge and then every other day for up to 15 days. Growth of sublethal doses of
Listeria monocytogenes, Mycobacterium bovis
(BCG Montreal),
M. tuberculosis
H37Rv, and
Salmonella enteritidis
in the livers and spleens of intravenously challenged mice was significantly increased compared with that in control animals receiving distilled water orally. Tilorone given every other day at a dosage of 10 mg/kg reduced (but did not completely ablate) the tuberculin response to the mycobacterial infections. Both tuberculin hypersensitivity and anti-mycobacterial resistance returned to normal values within days of stopping the drug treatment. Tilorone treatment at the 100-mg/kg dose level increased the growth of
S. enteritidis
in both intravenously and intragastrically challenged mice; this effect seemed to be due to the reduced ability of the host to express the normal granulomatous response to the microbial infection within the liver and spleen.
Rapid, Simple Bioassay for 5-Fluorocytosine in the Presence of Amphotericin B
Authors: Kaspar Robert L. , Drutz David J.
Published: June 2012

It is important that serum levels of 5-fluorocytosine (5FC) be measured to insure therapeutic levels while avoiding toxicity. This is particularly true in patients with renal insufficiency. The concurrent use of amphotericin B and 5FC complicates the measurement of 5FC in the serum, since fungi used in conventional bioassay systems are uniformly susceptible to amphotericin B. This paper describes the development of a simple, reliable, 6-h bioassay for 5FC in the presence of amphotericin B. The assay is based upon the fact that 5FC diffuses readily through yeast nitrogen base agar, whereas amphotericin B apparently does not. This assay allows rapid adjustments in therapy of patients receiving both 5FC and amphotericin B and has permitted us to maintain 5FC serum levels between limits of 25 and 120 μg/ml in patients with altered renal function.
Stimulation of Enzyme Synthesis by Sublethal Concentrations of Chloramphenicol Is Not Mediated by Ribonucleotide Pools
Authors: Ford Sharon R. , Switzer R. L.
Published: June 2012

Growth of
Salmonella typhimurium
LT-2 strain
pyrA81
in minimal medium containing 0.8 μg of chloramphenicol (CAP) per ml resulted in a 50 to 100% increase in the steady-state nucleotide pools in the cells. When such a culture was starved for uracil, the pyrimidine nucleotide pools decayed much more slowly in CAP-treated cells than in controls. An attempt was made to determine whether this effect of CAP on nucleotide pools could account for enhanced enzyme derepression observed under the same conditions (8). Treatment with low levels of puromycin also resulted in elevation of nucleotide pools but did not lead to enhanced enzyme synthesis. CAP treatment during arginine starvation has been shown to enhance enzyme synthesis, but nucleotide pools were not significantly affected by CAP nor was the stringent response relieved under these conditions. Thus, the effects of CAP on enzyme synthesis cannot be the result of effects of the antibiotic on nucleotide pools in all cases. The elevation of nucleotide pools was shown not to be due to enhanced conversion of exogeneous uracil into nucleotides, but to result from the enhanced turnover of ribonucleic acid in CAP-treated cells.
Empiric Therapy for Cancer Patients: Comparative Study of Ticarcillin-Tobramycin, Ticarcillin-Cephalothin, and Cephalothin-Tobramycin
Authors: Klastersky J. , Hensgens C. , Debusscher L.
Published: June 2012

Three combinations of antibiotics (cephalothin-tobramycin, cephalothin-ticarcillin, and ticarcillin-tobramycin) were administered empirically to 186 patients with cancer who were suspected of having a life-threatening infection. In approximately one-half of these patients, gram-negative infection was documented bacteriologically and consisted of septicemia in 50% of these patients. The three antimicrobial regimens were similarly effective and resulted in a favorable clinical response in approximately 55% of the patients. The administration of the cephalothin-tobramycin combination was associated with a significantly higher frequency of nephrotoxicity than that of the other two regimens.
Study of the Effects of Ticarcillin on Blood Coagulation and Platelet Function
Authors: Brown Clarence H. , Natelson Ethan A. , Bradshaw Major W. , Alfrey Clarence P. , Williams Temple W.
Published: June 2012

Ticarcillin is a new semisynthetic penicillin similar to carbenicillin. Since carbenicillin has been shown to inhibit platelet function to such an extent that bleeding may accompany its use, an investigation of the effects of ticarcillin on hemostasis was made. The drug was administered to 17 human volunteers for periods of 3 to 10 days in intravenous doses of 100, 200, or 300 mg/kg per day (7 to 21 g/day). Serial studies of blood coagulation and platelet function indicated that coagulation was unaffected by ticarcillin but that platelet function became defective in all subjects. Abnormal platelet function was evidenced by lengthening of bleeding time (17 of 17 volunteers), depressed adenosine diphosphate-induced platelet aggregation (17 of 17), defective collagen-induced aggregation (15 of 17), and abnormal epinephrine-induced aggregation (10 of 17). Prothrombin consumption, due to reduced platelet procoagulant activity, was significantly decreased with a dose of 300 mg/kg per day. Comparison of results from this study with those from an earlier carbenicillin study revealed that ticarcillin at 300 mg/kg per day produces the same defects in hemostasis as does carbenicillin at 300 mg/kg per day, but that lower doses (100 or 200 mg/kg per day) of ticarcillin result in only a mild defect in platelet function. If the effective dose of ticarcillin is proven to be lower than the doses of carbenicillin currently employed for treatment of certain gram-negative infections, bleeding should not be a frequent complication of ticarcillin administration, when the drug is given to patients with normal renal function.
Inhibition of the Growth of Hemadsorption 2 Virus by Three Acyl Derivatives of Amino Acids
Authors: Katz Ehud , Margalith Eva , Winer Bela
Published: June 2012

Three acyl derivatives of amino acids, dicarbobenzoxy-
l
-lysine sodium, carbobenzoxy-
l
-aspartic acid-β-benzyl ester potassium, and
N
-3-phenylpropionyl-S-benzyl-
l
-cysteine potassium inhibit the growth of parainfluenza 1 (hemadsorption 2) virus. The growth of simian virus 40, vaccinia, poliomyelitis type 1, Semliki Forest, Eastern equine encephalitis, and Western equine encephalitis viruses was not affected by these compounds. Four other acyl derivatives of amino acids did not inhibit the growth of any of the viruses tested.
Plasmid-Determined Resistance to Erythromycin: Comparison of Strains of
Streptococcus faecalis
and
Streptococcus pyogenes
with Regard to Plasmid Homology and Resistance Inducibility
Authors: Yagi Yoshihiko , Franke Arthur E. , Clewell Don B.
Published: June 2012

Streptococcus faecalis
strains DS-5 and
Streptococcus pyogenes
strain AC-1 both have a 17 million dalton plasmid that determines resistance to erythromycin, lincomycin, and vernamycin B
α
. The results of deoxyribonucleic acid-deoxyribonucleic acid hybridization experiments indicate that the two plasmids are about 95% homologous. It was also shown that erythromycin resistance is inducible in AC-1 and constitutive in DS-5.
Inhibition of Ribosomal A Site Functions by Sporangiomycin and Micrococcin
Authors: Cundliffe Eric , Dixon Peter D.
Published: June 2012

Sporangiomycin and micrococcin inhibit the binding of aminoacyl-transfer ribonucleic acid into the ribosomal A site in intact bacterial protoplasts. They also prevent the assembly of [ribosome-elongation factor G-guanine nucleotide] complexes in vitro and compete with [
35
S]thiostrepton for ribosomal binding sites. We conclude that micrococcin and sporangiomycin block the ribosomal A site in the vicinity of the complex guanosine triphosphatase center and so resemble thiostrepton in their modes of action.
Absorption of Pivampicillin in Postoperative Patients
Authors: Kunst M. W. , Mattie H.
Published: June 2012

The absorption of orally administered pivampicillin was studied in nine postoperative patients and compared with that of intravenously administered ampicillin. The absorption of pivampicillin was calculated on the basis of comparison of the areas under the serum concentration curves for both modes of administration. After an oral dose of 700 mg the absorption ranged from 40 to 95% (mean, 60%).
Incorporation of Double-Labeled
l
-Cystine and
dl
-Valine in Penicillin
Authors: Adriaens P. , Vanderhaeghe H. , Meesschaert B. , Eyssen H.
Published: June 2012

l
-[3,3′-
3
H]cystine was incorporated into penicillin with retention of one tritium. This result can be explained by β-lactam formation through ring closure between C3 of cysteine and NH of valine. No radioactivity of
dl
-[2,3-
3
H]valine was incorporated into penicillin. The loss of isotope at C2 occurs during the inversion of configuration. The loss of label at C3 is discussed in terms of possible intermediates for the formation of the thiazolidine ring of penicillin.
Fermentation, Isolation, and Antitumor Activity of Sterigmatocystins
Authors: Bradner W. T. , Bush J. A. , Myllymaki R. W. , Nettleton D. E. , O'Herron F. A.
Published: June 2012

In a screening program for antitumor substances from microbial fermentations, a compound was isolated from the mycelium of an
Aspergillus
species which proved to be the mycotoxin 5-methoxysterigmatocystin. This and the subsequently isolated sterigmatocystin gave significant inhibition of the transplanted mouse leukemias P-388 and L-1210. Preparation and testing of several derivatives of 5-methoxysterigmatocystin suggest that certain functions in the molecule are essential for tumor inhibition. Although slight antitumor effects have been reported for the chemically related aflatoxins, we believe this is the first report of antitumor activity of sterigmatocystins.
Feasibility of Administering Aminoglycoside Antibiotics by Continuous Intravenous Infusion
Authors: Bodey Gerald P. , Chang Hui-Yen , Rodriguez Victorio , Stewart Dorothy
Published: June 2012

Eleven patients each received gentamicin sulfate, tobramycin, and sisomicin by continuous intravenous infusion after an initial loading dose. Subsequent doses of antibiotic were adjusted in an attempt to maintain constant serum concentrations. There was considerable variation in the serum concentration from patient to patient and in the same patient from day to day with each drug. Although the dosages of gentamicin sulfate and tobramycin were similar, the serum concentrations of the latter drug were consistently lower. Despite the daily administration of doses of at least 300 mg of gentamicin and tobramycin per m
2
and 160 mg of sisomicin per m
2
, nephrotoxicity occurred in only three patients. This is a low frequency of nephrotoxicity, considering the dosages of drug administered. Although therapeutic efficacy was not an objective of this study, 8 of 11 documented infections were cured. This approach to the administration of aminoglycoside antibiotics deserves therapeutic trials.
Genetic and Physiological Studies on the Site of Action of Distamycin A
Authors: Siccardi A. G. , Lanza E. , Nielsen E. , Galizzi A. , Mazza G.
Published: June 2012

Two new genetic loci of
Bacillus subtilis
are identified by mutations that confer resistance to distamycin A and to other antibacterial agents. The chromosomal region where they map probably contains a cluster of genes whose products are related to membrane structure and function. Some of the biological effects of distamycin A are still in evidence in the resistant mutants indicating that the drug possibly acts at multiple sites. Most biological effects of the drug (including the phenotypic correction of a morphopoietic mutation) are likely to be due to the interaction of distamycin A with membrane (or surface) structures.
Production and Property of Beta-Lactamases in
Streptomyces
Authors: Ogawara Hiroshi
Published: June 2012

The production of β-lactamases by 100 strains of
Streptomyces
was studied. About one-half of the strains produced more than 2.3 U of β-lactamase per ml, and another half produced less than 1.4 U/ml. The amounts of β-lactamases produced by two strains were in the order of those produced by
Bacillus cereus
569/H and
Bacillus licheniformis
749/C. These
Streptomyces
enzymes function primarily as penicillinases rather than cephalosporinases. Properties such as pH optimum, substrate specificity, and heat stability suggest that these
Streptomyces
β-lactamases are closely related to each other. In contrast to bacterial β-lactamases,
Streptomyces
β-lactamases were insusceptible to inactivation by
N
-bromosuccinimide and only slightly susceptible to iodine. This suggests that the construction mode of the active site would be different from other β-lactamases. Studies on the minimum inhibitory concentrations of benzylpenicillin to seven
Streptomyces
strains and on their maximum β-lactamase production indicate that the susceptibility of
Streptomyces
to penicillin is not directly related to the β-lactamase production.
Simplified Method for Antimicrobial Susceptibility Testing of Anaerobic Bacteria
Authors: Fass Robert J. , Prior Richard B. , Rotilie Carol A.
Published: June 2012

A simple, abbreviated broth dilution test (tube test) utilizing a commercially available medium and inexpensive disposable materials, and which could be performed entirely in room air, was developed and used to test the susceptibility of 100 strains of anaerobic bacteria to clindamycin, chloramphenicol, ampicillin, and tetracycline. Results are reported in categories of susceptibility: susceptible to concentrations surpassed in vivo with usual dosage, susceptible to concentrations surpassed in vivo with high dosage, and resistant to concentrations achievable in vivo. Results are compared to minimal inhibitory concentrations which were determined simultaneously by using a microdilution method in an anaerobic glove box. Twenty strains of
Bacteroides fragilis
, 10 strains of
Fusobacterium
, 20 strains of
Clostridium
, 10 strains of gram-positive non-sporeforming bacilli, and 30 strains of cocci grew to visible turbidity within 1 day of incubation. Of the 360 antibiotic-organism combinations tested, 98% were in a susceptibility category that corresponded (within one concentration) to the actual minimal inhibitory concentration as determined by the microdilution method. After 2 days of incubation, growth was more abundant, but results often indicated inappropriate degrees of resistance. Variation in inoculum size had little effect on results. Ten strains of
B. melaninogenicus
did not grow enough for susceptibility to be categorized accurately. The tube test could be used in any clinical microbiology laboratory for a limited number of susceptibility tests on anaerobic bacteria other than
B. melaninogenicus
without preparation of special media or purchase of special equipment.
Comparative In Vitro Activity and Clinical Pharmacology of Ticarcillin and Carbenicillin
Authors: Neu Harold C. , Garvey Glenda J.
Published: June 2012

The in vitro activity and human pharmacology of ticarcillin, a semisynthetic penicillin more active than carbenicillin against
Pseudomonas
, were compared. There has been no increase in resistance to ticarcillin of
Pseudomonas
strains over the past 5 years, but resistance of indole-positive
Proteus
and
Serratia
strains has been documented. After intramuscular (i.m.) injection of 1 g of ticarcillin, mean peak levels occurred at 1 h (26.9 μg/ml) with a decline over 6 h (6.8 μg/ml). Serum half-life was 84 min. Dilution of ticarcillin lidocaine reduced pain on i.m. injection but did not alter serum levels. Blood levels after 1 g i.m. are adequate to treat infections produced by
Escherichia coli, Proteus mirabilis
, and some
Enterobacter
, but not
Pseudomonas
. After rapid intravenous infusion of 3 and 5 g, mean peak serum levels of ticarcillin were slightly lower for 1 h than those achieved with carbenicillin. Probenecid administered before infusion produced increases in blood levels, half-lives, and volume of distribution. The biological half-life of ticarcillin was 72 min compared to 66 min with carbenicillin. There was a larger volume of distribution for ticarcillin than carbenicillin (15 liters versus 14 liters). The ticarcillin half-life when administered with probenecid was 108 min. Urinary recovery of ticarcillin was 77% against 95% of carbenicillin. However, approximately 10% of ticarcillin is recovered as penicilloic acid so that 95% of an intravenously administered dose is recovered.
Inhibition of Protein Synthesis in Intact HeLa Cells
Authors: Tscherne Joan S. , Pestka Sidney
Published: June 2012

Polysome analysis has proved to be a sensitive probe for the mode of action of inhibitors of protein synthesis in intact HeLa cells. To classify the active compounds as inhibitors of initiation, elongation, or termination, their effects on the cellular polyribosome pattern were compared under three conditions. These conditions tested (i) their direct effect on the polyribosome profile; (ii) their effect on ribosome run-off produced by hypertonicity; and (iii) their effects on recovery from hypertonicity. Using this technique, diacetoxyscirpenol, 2-(4-methyl-2,6-dinitroanilino)-
N
-methylpropionamide, and three alkaloids, harringtonine, isoharringtonine, and homoharringtonine, were found to be inhibitors of initiation. Polysome analysis indicated that in HeLa cells 7.8 × 10
−7
M pactamycin, which inhibited protein synthesis 94%, interfered with elongation as well as initiation under these conditions. Emetine, anisomycin, cycloheximide, and trichodermin each gave polysome patterns consistent with inhibition of elongation. Fusidic acid and aurintricarboxylic acid inhibited incorporation of [
14
C]leucine into intact HeLa cells, but polysome analysis did not localize any specific inhibitory effects to the initiation, elongation, or termination steps of protein synthesis. The use of specific inhibitors of initiation of protein synthesis has indicated that most, if not all, mammalian messenger ribonucleic acids contain a single initiation site.
Bacampicillin: a New Orally Well-Absorbed Derivative of Ampicillin
Authors: Bodin N.-O. , Ekström B. , Forsgren U. , Jalar L.-P. , Magni L. , Ramsay C.-H. , Sjöberg B.
Published: June 2012

Bacampicillin (proposed international nonproprietary name), 1′-ethoxycarbonyloxyethyl 6-(
d
-α-aminophenylacetamido)penicillanate, is a new orally well-absorbed penicillin, highly active in vivo due to rapid transformation into ampicillin. The compound is stable in vitro at gastric pH and hydrolyzed slowly to ampicillin at neutral pH but very rapidly in the presence of biological fluids, e.g., tissue homogenates or serum. In vivo the transformation into ampicillin is so rapid that no unchanged compound could be detected in the blood after oral administration of bacampicillin to rats, dogs, and humans. On oral administration to mice, rats, and dogs, bacampicillin was found to be better absorbed than ampicillin, giving higher and earlier peak blood levels of ampicillin. The bioavailability of bacampicillin in rats and dogs was three to four times higher than that of an equimolar amount of ampicillin. On oral administration to rats, bacampicillin was found to give higher levels of ampicillin in organs such as the kidney, liver, and spleen than ampicillin itself. In “tissue cages” in rats, higher transudate levels of antibiotic were found after oral administration of bacampicillin than after ampicillin. On oral treatment of experimentally infected mice, bacampicillin was found to be more active than ampicillin.
Monophenol Monooxygenase and Lincomysin Biosynthesis in
Streptomyces lincolnensis
Authors: Michalik Joanna , Emilianowicz-Czerska Władysława , Switalski Lech , Raczynska-Bojanowska Konstancja
Published: June 2012

Monophenol monooxygenase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase EC 1.14.18.1) was studied in melanin-positive and melanin-negative mutants of
Streptomyces lincolnensis
NCIB 9413, varying in the lincomycin synthesizing ability. The activities of laccase and tyrosine phenol lyase (EC 4.1.99.2) are absent in this organism. The monophenol monooxygenase catalyzes hydroxylation of monophenols (

K
m

and
V
max
for
l
-tyrosine, 2 × 10
−4
M and 8.0 nmol of O
2
/min per ml, respectively) at a slower rate than it dehydrogenates diphenols to
o
-quinones (

K
m

and
V
max
for
l
-3,4-dihydroxyphenylalanine, 7 × 10
−5
M and 51.7 nmol of O
2
/min per ml, respectively. It is inhibited by KCN, β-mercaptoethanol, ethylenediaminetetraacetate, dipyridyl, thiourea,
p
-aminobenzoic acids and by some tryptophan metabolites. Changes in the activity of monophenol monooxygenase caused by mutation or by inhibitors are reflected in the synthesis of the antibiotic. Its participation in the biogenesis of the propylhygric moiety of lincomycin is discussed.
Effect of Peritoneal Dialysis on Serum Levels of Tobramycin and Clindamycin
Authors: Malacoff Robert F. , Finkelstein Frederic O. , Andriole Vincent T.
Published: June 2012

The pharmacokinetics of tobramycin and clindamycin were examined in patients undergoing peritoneal dialysis for chronic renal failure. Peak serum levels of tobramycin in functionally anephric patients were less than expected, probably secondary to a larger volume of distribution. Peritoneal dialysis resulted in a significant clearance of tobramycin, with a resultant reduction in serum half-life. The present data suggest that, if bactericidal serum levels of tobramycin are to be maintained in patients undergoing peritoneal dialysis, a parenteral loading dose be administered, followed by either (i) an identical dose every third half-life or (ii) one-half the loading dose every half-life. However, optimal therapy is best achieved by monitoring serum levels to insure appropriate drug dosage. Peak serum levels of clindamycin in functionally anephric patients were approximately twofold greater than those expected in normals after an identical parenteral dose. It is, therefore, recommended that the administered dose of this agent in functionally anephric patients be one-half of that required to produce desired peak serum levels in patients without renal impairment. Peritoneal clearance of clindamycin during dialysis was shown to be essentially zero, indicating that dialysis does not affect clindamycin disposition.
Detection of Temperature-Sensitive Tetracycline Resistance Plasmids in
Staphylococcus aureus
Authors: May J. W. , Houghton R. H. , Perret C. J.
Published: June 2012

A method is described for the detection of temperature-sensitive plasmids determining tetracycline resistance in
Staphylococcus aureus
. Temperature-sensitive plasmids were detected in phage group I strains but not in phage group III strains.
Inhibitory Effect of Colicin E
2
on Transport Systems of
Escherichia coli
in the Presence of the
rex
Gene of λ Prophage
Authors: Beppu Teruhiko , Yamamoto Hirokazu , Arima Kei
Published: June 2012

Purified colicin E
2
was found to cause marked inhibition of the permeation rate of
o
-nitrophenyl-galactoside (ONPG) in several λ-lysogenic strains of
Escherichia coli
in the presence of chloramphenicol to prevent prophage induction. The inhibitory effect of colicin E
2
on transport systems was analyzed with cells of
E. coli
CP78(λ). The dose of colicin E
2
for the half-maximum inhibition of the ONPG-permeation rate was about 9 molecules of the colicin per bacterium under the aerobic condition, which corresponded to about 1 killing unit per bacterium. Kinetics of the transport of [
14
C]methylthiogalactoside suggested that colicin E
2
began to inhibit the influx rate of β-galactosides within a few minutes after the colicin addition, and the maximum inhibition reached more than 80%. Extensive leakage of intracellular potassium ion and inhibition of
l
-proline transport also occurred at the same time. Acid solubilization of cellular deoxyribonucleic acid by the colicin was apparently delayed to the initiation of the transport inhibition. The extents of the inhibition of β-galactoside transport and leakage of potassium ion by the colicin were extensive in cells lysogenic for wild λ phage or λ
ind
−
, whereas the extents were slight in the nonlysogenic cells or cells carrying λ
rex
−
prophage. It was concluded that the sensitization of membrane transport systems of
E. coli
cells to colicin E
2
was achieved by the presence of the
rex
gene product of λ phage.
Effect of Temperature on the Rate of the Transparent to Opaque Colony Type Transition in
Mycobacterium avium
Authors: Woodley Charles L. , David Hugo L.
Published: June 2012

The results of drug susceptibility tests were found to be affected by changes that occur spontaneously in populations of
Mycobacterium avium
maintained in the laboratory. Because the transparent colony type variant was resistant to antituberculosis chemotherapeutic agents and the opaque colony type variant was usually susceptible to these agents, the transition of transparent to opaque colony type was investigated. The rate of the transition was found to be temperature dependent and, in agreement with a previous report, was found to be about 10
−4
to 10
−5
per generation at 37 C. Reversion was found to occur at a rate of 10
−6
to 10
−7
at 37 C. The mutation rate from susceptibility to resistance to rifampin, kanamycin, and erythromycin was about 10
−8
to 10
−9
mutations per bacterium per generation. Judged from our data, the high rate of the transparent to opaque variation was not caused either by mutator effects or by the occurrence of extrachromosomal genes in these bacteria, but could have been due to selective mechanisms still incompletely understood.
Bone Concentrations of Antimicrobial Agents After Parenteral Administration
Authors: Smilack Jerry D. , Flittie William H. , Williams Temple W.
Published: June 2012

Bone concentrations of seven antimicrobial agents were determined after parenteral administration. Antibiotics were administered in large doses at customary intervals for 12 to 20 h before total hip or knee replacement; anticipated levels of each drug were achieved in the serum. Methicillin, carbenicillin, and clindamycin were detected in bone with greatest frequency. Cefazolin and gentamicin were each detected in bone specimens from only one of four patients. Neither penicillin G nor cephalothin was present in bone in sufficient quantity to be measurable. These data suggest that a number of factors, in addition to serum concentration, affect concentration of antimicrobial agents in bone. The clinical significance of the relationship between bone concentrations of antibiotics and therapeutic outcome is not certain.
Protective Effect of Cephalothin Against Gentamicin-Induced Nephrotoxicity in Rats
Authors: Dellinger Patchen , Murphy Terrence , Pinn Vivian , Barza Michael , Weinstein Louis
Published: June 2012

The possibility that the nephrotoxicity of gentamicin may be potentiated by the concomitant administration of cephalothin was examined in a rat model. Cephalothin given once daily in dosages up to 800 mg/kg per day for 10 days produced no renal damage. Gentamicin, at 6 to 50 mg/kg per day, caused pathological changes which were dosage related and affected primarily the proximal tubular cells. Administration of the two drugs simultaneously resulted in a significant protective effect of cephalothin against gentamicin-related nephrotoxicity (
P
< 0.01). When the daily injections of the two agents were separated by an interval of 6 h, the protective effect was lost, and the resultant damage was the same as that due to gentamicin alone. The protective effect of cephalothin was reproduced by the administration of equiosmolar amounts of sulfate (sodium sulfate), suggesting that the phenomenon might be related to the presence of nonresorbable anion in the urine. These studies indicate that, in the rat, cephalothin does not potentiate, but, in fact, may prevent the nephrotoxic effects of gentamicin.
Plasmid-Mediated Penicillin Beta-Lactamases in
Pseudomonas aeruginosa
Authors: Sawada Yosuke , Yaginuma Satoshi , Tai Masaru , Iyobe Shizuko , Mitsuhashi Susumu
Published: June 2012

A penicillin β-lactamase (PCase) was extracted from
Pseudomonas aeruginosa
Rms139
+
and purified by means of column chromatography. The isoelectric point of Rms139 PCase was 5.7 and its molecular weight was 22,500 ± 1,000. The optimal pH for the hydrolysis of benzylpenicillin was 7.0 to 7.5 and the optimal temperature was 45 C, with the PCase also showing high activity against carbenicillin. It is concluded that this enzyme is a new type of penicillin β-lactamase different from the type I, II, or III R plasmid-mediated PCases reported previously.
Drug Resistance and Distribution of R Factors in
Salmonella
Strains
Authors: Tanaka Tokumitsu , Ikemura Kengo , Tsunoda Mitsuko , Sasagawa Itaru , Mitsuhashi Susumu
Published: June 2012

Drug resistance and the distribution of R factors in
Salmonella
strains were surveyed using 1,980 strains isolated in Japan from 1955 to 1973. Resistances were mostly restricted to sulfanilamide (SA), tetracycline (TC), and streptomycin (SM), and combinations thereof. The demonstrated frequency of strains resistant to chloramphenicol (CM) was very low as compared with that in
Escherichia coli
and
Shigella
strains. In relation to resistance to TC, CM, SM and SA, the frequency of isolation of single resistance was the highest, followed by triple, double, and quadruple resistance in that order. Low frequency of isolation of quadruple resistance was due to the low frequency of CM resistance in
Salmonella
strains and differed from the
E. coli
or
Shigella
group. R factors with single TC resistance was most common, followed by those with TC,SM,SA; SM,SA; TC,CM,SM,SA; and single (SM and SA) resistance, in that order. Kanamycin and ampicillin resistance was unusual and mostly transmissible.
Production, Isolation, and Properties of Azetomycins
Authors: Formica Joseph V. , Apple Martin A.
Published: June 2012

Streptomyces antibioticus
synthesizes five actinomycins that differ in the “proline site” of the molecule. When cultured in the presence of azetidine-2-carboxylic acid (AzC), antibiotic synthesis was stimulated 40 to 50%, synthesis of actinomycin IV was inhibited, and one or both prolines were replaced by AzC. AzC incorporation could not be reversed by concomitant supplementation with proline or sarcosine, and only pipecolic acid affected a minor reversal of AzC incorporation. AzC-containing actinomycins were isolated and designated azet-I and azet-II; a third unresolved component or mixture was called azet-III. The molar ratio of AzC to proline was: azet-I, 1:1; azet-II, 2:0. Azet-III was equivocal. These azetidine actinomycins (azetomycins) were found to be potently inhibitory to the growth of selected gram-positive but not as potent to the growth of gram-negative organisms. The relative inhibitory affect against growth and ribonucleic acid synthesis in
Bacillus subtilis
was: actinomycin IV azet-I > azet-II >>> azet-III. Protein synthesis was affected similarly; however, kinetic studies with
B. subtilis
revealed that ribonucleic acid synthesis was inhibited rapidly followed by an inhibition of protein synthesis. At concentrations less than 1 μg/ml, deoxyribonucleic acid synthesis was stimulated by these actinomycins.
Antiviral Activity of 10-Carboxymethyl-9-Acridanone
Authors: Kramer M. J. , Cleeland R. , Grunberg E.
Published: June 2012

Intraperitoneal administration of 10-carboxymethyl-9-acridanone sodium salt (CMA) protected at least 50% of mice tested from otherwise lethal infections with Semliki forest, coxsackie B1, Columbia SK, Western equine encephalitis, herpes simplex, and pseudorabies viruses. The protective effect against influenza A2/Asian/J305 and coxsackie A21 viruses was less but was statistically significant. When administered either subcutaneously or orally, CMA protected at least 50% of mice against Semliki forest and pseudorabies viruses; the effect against coxsackie B1 and herpes simplex viruses was less but was statistically significant. Initiation of treatment could be delayed from 2 to 24 h after infection of mice with coxsackie B1, herpes simplex, Semliki forest, and Western equine encephalitis viruses without loss of an antiviral effect. CMA did not inactivate Semliki forest or coxsackie B1 viruses on contact and was without effect against any of the viruses tested in tissue culture by the tube dilution assay. The humoral antibody response in mice to both influenza virus and sheep erythrocytes was unaffected by CMA. After administration of CMA, an interferon-like substance was induced in mice or mouse cell culture but not in rabbits or rabbit cell culture.
Rosamicin: In Vitro Activity Against Anaerobes and Comparison with Erythromycin
Authors: Sutter Vera L. , Finegold Sydney M.
Published: June 2012

The in vitro activity of rosamicin was determined against 231 strains of anaerobic bacteria and compared with the activity of erythromycin against the same strains. Rosamicin and erythromycin had similar activity against strains of
Peptostreptococcus
and gram-positive nonsporeforming bacilli. Rosamicin was somewhat more active against strains of
Peptococcus, Clostridium
, and gram-negative anaerobes. All strains of
Bacteroides fragilis
tested were inhibited by 4 μg of rosamicin or less per ml, whereas only 76% of them were inhibited by this concentration of erythromycin. Rosamicin was distinctly more active against
Fusobacterium nucleatum
. Because of its in vitro activity, further investigation of the pharmacology of this drug is warranted.
Killing of
Torulopsis glabrata
by
Saccharomyces cerevisiae
Killer Factor
Authors: Bussey Howard , Skipper Nigel
Published: June 2012

The
Saccharomyces cerevisiae
killer factor glycoproteins killed the pathogen
Torulopsis glabrata
by a mechanism involving membrane damage. Some other yeast species were unaffected by these glycoprotein toxins.
Simple Assay for 5-Fluorocytosine in the Presence of Amphotericin B
Authors: Kauffman Carol A. , Carleton Judith A. , Frame Peter T.
Published: June 2012

A simple method for the measurement of 5-fluorocytosine in the presence of amphotericin B is described. The antifungal activity of amphotericin B is abolished by heating serum at 100 C for 45 min. 5-Fluorocytosine is unaffected by this treatment, and serum levels can be subsequently assayed by either tube dilution or disk diffusion methods.