bluuebunny/crossref_metadata_2025 huggingface dataset:
Active Insolubilized Antibiotics Based on Cellulose and Cellulose Carbonate
Authors: Kennedy J. F. , Tun H. Cho
Published: June 2012

The coupling of a number of antibiotics to cellulose and cellulose
trans
-2,3-carbonate under a series of coupling conditions has been investigated, and it has been shown that by such couplings active insoluble derivatives of antibiotics can be produced. It was found that the antibiotics became firmly bound to cellulose itself, whereas use of cellulose carbonate extended the range of antibacterial activity retained. In the case of cellulose, it was considered that physical adsorption phenomena were operating, whereas a covalent bond was more likely in the case of cellulose carbonate where the antibiotic amino groups could attack the electrophilic cyclic carbonate carbon atoms. The release of antibiotic from the matrix during testing of antibacterial activity was likely due to the action of a cellulase or additionally an esterase in the case of cellulose carbonate. The importance and potential of these new types of chemical derivatives are discussed in terms of new outlets for the commerical use of cellulose.
Use of Gentamicin in the Isolation of Subgroup A
Chlamydia
Authors: Wentworth Berttina B.
Published: June 2012

The use of gentamicin to control contamination in a tissue culture system for the isolation of
Chlamydia
was investigated. Gentamicin, at concentrations up to 100 μg/ml, did not appear to inhibit the growth of stock chlamydial strains, as judged by assays for iodine-staining inclusions. When 343 cervical and urethral specimens were examined in the presence and in the absence of gentamicin, significantly more isolations of chlamydiae were obtained in the presence of 10 μg of gentamicin/ml, and significantly fewer unsatisfactory results due to contaminating organisms were seen. Therefore, this aminoglycoside antibiotic appears to be a useful addition to a cell system for isolation of
Chlamydia
.
Novel sulfated polymers as highly potent and selective inhibitors of human immunodeficiency virus replication and giant cell formation
Authors: Baba M , Schols D , De Clercq E , Pauwels R , Nagy M , Györgyi-Edelényi J , Löw M , Görög S
Published: June 2012

Novel synthetic sulfated polymers, namely, sulfated polyvinyl alcohol (PVAS) and sulfated copolymers of acrylic acid with vinyl alcohol (PAVAS), proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in vitro. The compounds completely inhibited HIV-1-induced cytopathogenicity in MT-4 cells and HIV-1 antigen expression in CEM cells at a concentration of 0.8 micrograms/ml. They were equally effective against HIV-2 replication. In addition, and in contrast to azidothymidine, PAVAS and PVAS suppressed HIV-1-induced giant cell (syncytium) formation, a process that may account for the depletion of T4 lymphocytes in patients with acquired immunodeficiency syndrome. PAVAS and PVAS completely blocked giant cell formation at a concentration of 4 micrograms/ml, whereas for dextran sulfate a concentration of 100 micrograms/ml was required to achieve complete inhibition of giant cell formation. As has been demonstrated previously for the sulfated polysaccharides, the mechanism of action of PAVAS and PVAS resides in the inhibition of virus adsorption to the cells.
Critical hydrogen bonding by serine 235 for cephalosporinase activity of TEM-1 beta-lactamase
Authors: Imtiaz U , Manavathu E K , Lerner S A , Mobashery S
Published: June 2012

The role of Ser-235 in the catalytic mechanism of the TEM-1 beta-lactamase has been explored by the study of a mutant enzyme in which Ser-235 has been substituted by alanine (Ala-235 mutant enzyme). A comparative kinetic analysis of both the wild-type and the Ala-235 TEM-1 enzymes revealed little effect of this substitution of residue 235 on the turnover of penicillins but a greater effect on the turnover of cephalosporins. Susceptibility testing of Escherichia coli strains harboring the wild-type TEM-1 beta-lactamase and the Ala-235 mutant enzyme revealed an effect of the mutation similar to that observed in the enzymological studies. The MICs of two representative cephalosporins for the strain containing the mutant enzyme were much lower than those for the isogenic strain bearing the wild-type TEM-1 beta-lactamase. On the other hand, the strain with the mutant enzyme was still highly resistant to penicillins.
PCR mapping of integrons reveals several novel combinations of resistance genes
Authors: Lévesque C , Piché L , Larose C , Roy P H
Published: June 2012

The integron is a new type of mobile element which has evolved by a site-specific recombinational mechanism. Integrons consist of two conserved segments of DNA separated by a variable region containing one or more genes integrated as cassettes. Oligonucleotide probes specific for the conserved segments have revealed that integrons are widespread in recently isolated clinical bacteria. Also, by using oligonucleotide probes for several antibiotic resistance genes, we have found novel combinations of resistance genes in these strains. By using PCR, we have determined the content and order of the resistance genes inserted between the conserved segments in the integrons of these clinical isolates. PCR mapping of integrons can be a useful epidemiological tool to study the evolution of multiresistance plasmids and transposons and dissemination of antibiotic resistance genes.
Nonspecific Ionic Inhibition of Ethambutol Binding by
Mycobacterium smegmatis
Authors: Beggs William H. , Andrews Fred A.
Published: June 2012

Magnesium sulfate and spermidine were tested for their effects on binding of
14
C-ethambutol by
Mycobacterium smegmatis
. Concentrations were used that protected the organism from ethambutol inhibition. Sodium salts were examined as possible ethambutol antagonists to test the previously reported specificity of the divalent cation salt effect. Consistent with growth-protection experiments, 20 mM MgSO
4
or 2.0 mM spermidine prevented and reversed
14
C binding by cells shaken with 0.2 μg of
14
C-ethambutol per ml of Sauton medium at 37 C. Sodium salts were not effective ethambutol antagonists when tested at 20 mM, but at concentrations equivalent in ionic strength (μ) to that provided by 20 mM MgSO
4
they were effective. Thus, 20 mM MgSO
4
, 80 mM NaCl, or 27 mM Na
2
SO
4
(μ = 0.08) all gave similar results in growth protection and binding experiments, suggesting that MgSO
4
antagonism is a nonspecific ionic effect. Because spermidine (μ ≤ 0.012) antagonized ethambutol at an ionic strength substantially less than that required for the metal salts, its effect may hinge on structural similarity to ethambutol rather than its cationic character. Drug and polyamine may compete for one site or a heterogeneous group of binding sites involving adsorption, transport, and intracellular target reactions. Until we know at which of these levels spermidine antagonizes ethambutol binding, the relationship between polyamines and ethambutol action will remain obscure. However, these studies have weakened the earlier argument for a divalent cation-requiring system as a specific ethambutol target site.
Chemical Modification of Maridomycin, a New Macrolide Antibiotic
Authors: Harada Setsuo , Muroi Masayuki , Kondo Masahiro , Tsuchiya Kanji , Matsuzawa Tai , Fugono Takeshi , Kishi Toyokazu , Ueyanagi Jisaburo
Published: June 2012

Maridomycin, a new macrolide antibiotic, and tetrahydromaridomycin were acylated into their mono, di, and tri acyl derivatives.

These derivatives were compared with the parent antibiotic, maridomycin, for their (i) in vitro antimicrobial activities, (ii) protective effect in mice infected with
Staphylococcus aureus
(oral administration), (iii) blood levels attained in rats, and (iv) acute toxicity in mice (intraperitoneal administration). All the derivatives showed either the same or less activity in vitro, but 9-acyl, 9, 2′-diacylmaridomycin and 9, 13, 2′-triacetyltetrahydromaridomycin demonstrated improved therapeutic effects together with higher blood levels and low toxicity. 9-Propionylmaridomycin showed the most favorable biological properties.
Fluid and Pharmacological Dynamics in a Subcutaneous Chamber Implanted in Rats
Authors: Gardner William G. , Prior Richard B. , Perkins Robert L.
Published: June 2012

Antibiotic dynamics in the fluid obtained from subcutaneously implanted chambers in rats were similar to those observed in serum following single intramuscular injections of carbenicillin.
Isolation of Regulatory Mutants of the Aspartic and Pyruvic Acid Families and Their Effect on Antibiotic Production in
Streptomyces lipmanii
Authors: Godfrey Otis W.
Published: June 2012

Streptomyces lipmanii
L100 produces two β-lactam ring-containing antibiotics: penicillin N and 7-(5-amino-5-carboxy valeramido)-7-methoxy-cephalosporanic acid. These antibiotics are modified tripeptides derived from α-aminoadipic acid, cysteine, and valine. Mutants defective either in the biosynthesis or in the control of amino acids belonging to the aspartic and pyruvic acid families were isolated and characterized with regard to their effect on antibiotic synthesis. In a number of these mutants antibiotic synthesis was either completely inhibited or increased up to threefold over wild-type levels.
Protein Synthesis in
Mycobacterium tuberculosis
H37Rv and the Effect of Streptomycin in Streptomycin-Susceptible and -Resistant Strains
Authors: Shaila M. S. , Gopinathan K. P. , Ramakrishnan T.
Published: June 2012

An efficient in vitro amino acid-incorporating system from
Mycobacterium tuberculosis
H37Rv was standardized. Ribonucleic acid (RNA) isolated from phage-infected
M. smegmatis
cells served as natural messenger RNA and directed the incorporation of
14
C-amino acids into protein. The effects of various antitubercular drugs and “known inhibitors” of protein synthesis on amino acid incorporation were studied. Antibiotics like chloramphenicol and tetracycline inhibited mycobacterial protein synthesis, though they failed to prevent the growth of the organism. This failure was shown to be due to the impermeability of mycobacteria to these drugs by use of “membrane-active” agents along with the antibiotics in growth inhibition studies. Several independent streptomycin-resistant mutants of
M. tuberculosis
H37Rv were isolated. Streptomycin inhibited the incorporation of
14
C-amino acids into proteins by whole cells of a streptomycin-susceptible strain by more than 90%, whereas very little or no inhibition was observed in either high-level or low-level streptomycin-resistant strains.

In vitro, streptomycin was an effective inhibitor of susceptible strains, whereas in streptomycin-resistant strains the concentration of streptomycin at which half-maximal inhibition was produced varied according to the resistance of whole cells, and there was a correlation between the two. In one low-level streptomycin-resistant mutant, the in vitro amino acid-incorporating system was as sensitive to various concentrations of streptomycin as the parental type, and a possible involvement of a membrane site in the development of low-level resistance was indicated. Streptomycin susceptibility and high-level resistance were shown to be ribosomal in nature.
Bacteriocin of a Group A Streptococcus: Partial Purification and Properties
Authors: Tagg J. R. , Read R. S. D. , McGiven A. R.
Published: June 2012

The production of bacteriocin-like inhibition by certain strains of group A streptococci was demonstrated during the growth of these organisms on solid nutrient media. Active bacteriocin could not be recovered from broth cultures, possibly because of its inactivation by streptococcal proteinase. The bacteriocin, streptocin A, produced by
Streptococcus pyogenes
strain FF-22 was partially purified by chemical precipitation and chromatography on carboxymethyl-cellulose. Streptocin A inhibited the growth of various gram-positive organisms but none of a wide range of different gram-negative strains. The bacteriocin was inactivated by proteolytic enzymes and, although labile in alkali, it was extremely stable to heating in mild acids.
Action of 12 Tetracyclines on Susceptible and Resistant Strains of
Staphylococcus aureus
Authors: Sompolinsky David , Krausz Judith
Published: June 2012

The relative growth inhibition caused by 12 tetracyclines in a susceptible strain of
Staphylococcus aureus
(111-elim) and in the same strain carrying a resistance-plasmid (111) showed entirely different patterns. For four of the tetracyclines (minocycline, anhydrotetracycline, chelocardin, and desdimethylaminotetracycline), the strain with the tetracycline plasmid (111) had virtually the same tolerance as the susceptible strain (111-elim). A resistant mutant of strain 111-elim showed a third pattern of relative growth inhibition, and another distinct pattern was observed in a veterinary wild strain of
S. aureus
. Of the 12 tetracyclines, 11 were effective inducers of higher tetracycline resistance in
S. aureus
111, but no correlation was found between the efficacy of the tetracyclines as inducers and as inhibitors of growth of 111-elim or 111. At external drug concentrations causing doubling of the generation time (

K
i

), 111-elim accumulated tetracycline, oxytetracycline, and minocycline to a degree corresponding to several thousand molecules per coccus. At a fixed external drug concentration, 111 accumulated less tetracycline and oxytetracycline than 111-elim, whereas comparison at their respective

K
i

values showed accumulation to be significantly higher for 111 than for 111-elim. The accumulation of tetracyclines is assumed to involve both surface sorption and active membrane transport. Resistance is probably due to decreased accumulation of the drugs, and a hypothesis explaining the mechanism of resistance is offered.
Synthesis of Cephalosporin C from Sulfate by Mutants of
Cephalosporium acremonium
Authors: Niss H. F. , Nash C. H.
Published: June 2012

The innate ability of
Cephalosporium acremonium
to use methionine preferentially over sulfate for synthesis of cephalosporin C can be influenced through mutation. Mutants of
C. acremonium
with altered capacity to utilize sulfate for synthesis of antibiotic were isolated and partially characterized with respect to the uptake of sulfate and the regulation of arylsulfatase.
Studies on the Mechanism of Action of Nalidixic Acid
Authors: Bourguignon Gerard J. , Levitt Martin , Sternglanz Rolf
Published: June 2012

With three independent techniques (absorption spectrophotometry, measurement of the deoxyribonucleic acid [DNA] melting temperature, and equilibrium dialysis), no evidence has been found for the binding of nalidixic acid to purified DNA. Also, no evidence has been found to support the hypothesis that nalidixic acid is permanently modified to a new, active compound by the bacterial cell. By using an in vitro DNA replication system developed by Bonhoeffer and colleagues, soluble extracts from nalidixic acid-sensitive cells have been shown to confer nalidixic acid sensitivity on the DNA synthesis of lysates from nalidixic acid-resistant cells. The activity in the extracts is only present in sensitive cells and is nondialyzable and heat sensitive. Finally, two known nalidixic acid-resistant mutants of
Escherichia coli
, mapping at
nal A
and
nal B
, respectively, have been tested to determine whether either of them is a transport mutant. It has been shown that
nal B
r
is a transport mutant whereas
nal A
r
is not.
Rapid Gentamicin Bioassay Using a Multiple-Antibiotic-Resistant Strain of
Klebsiella pneumoniae
Authors: Lund Marlys E. , Blazevic Donna J. , Matsen John M.
Published: June 2012

A rapid bioassay for gentamicin levels in serum was developed by using a strain of
Klebsiella pneumoniae
that has multiple resistance to antibiotics. Assays were comparable when performed on either small or large petri plates, and results were available in 2 to 4 h. Studies showed an overall recovery of 97.6% for gentamicin alone or 104.5% in the presence of commonly used antibiotics. The procedure can be performed without the need to inactivate other antibiotics that may be present in the serum sample.
Salmonella typhi
resistant to Chloramphenicol, Ampicillin, and Other Antimicrobial Agents: Strains Isolated During an Extensive Typhoid Fever Epidemic in Mexico
Authors: Olarte Jorge , Galindo Emma
Published: June 2012

During 1972 a large epidemic, in excess of 10,000 cases, of typhoid fever occurred in Mexico City, Pachuca, and other communities of Mexico. The main characteristic of the epidemic, in addition to the large number of persons affected, was the prevalence of a strain of
Salmonella typhi
which was highly resistant to chloramphenicol both in vivo and in vitro, and which belonged to a single phage type, Vi degraded approaching type A. Of 493 strains of
S. typhi
studied during the outbreak, 452 (91.7%) were resistant to chloramphenicol (CM), tetracycline (TC), streptomycin (SM), and sulfonamides (SU). The epidemic strain owes its resistance to an R factor which is easily transferable to
Escherichia coli
K-12 and which appears to be stable. In the third month of the outbreak, a strain of
S. typhi
resistant to CM, TC, SM, SU, ampicillin (AM), and kanamycin (KM) was isolated from a patient with severe typhoid fever. During the following 9 months, six additional strains of
S. typhi
resistant to AM, CM, TC, SM, and SU were also isolated. Transfer experiments to
E. coli
K-12 indicate that these strains are infected with two different R factors, one causing CM, TC, SM, and SU resistance and the other causing AM or AM and KM resistance. The frequency of transfer of the resistance in overnight crosses was in the order of 10
−4
for CM, TC, SM, and SU and 10
−6
for AM or AM, and KM. The appearance of these strains resistant both to chloramphenicol and ampicillin was a cause for concern for the clinicians; fortunately, they have remained an infrequent cause of disease.
Disk Susceptibility Studies with Cefazolin and Cephalothin
Authors: Actor Paul , Guarini Joseph , Uri Joseph , Dickson Judith , Pauls John F. , Weisbach Jerry A.
Published: June 2012

Cefazolin and cephalothin disk susceptibility and minimal inhibitory concentration determinations were conducted on 591 clinical isolates. Cefazolin demonstrated superior activity, as shown by lower minimal inhibitory concentrations, and a greater percentage of isolates inhibited in the disk susceptibility test. The cephalothin antibiotic class disk by the standard Bauer-Kirby method failed to detect susceptibility to cefazolin in a significant percentage of
Escherchia coli, Enterobacter
species, and
Enterococcus
isolates. A separate cefazolin disk with a susceptibility cut-off point of 18 mm is recommended. An alternative to a separate cefazolin disk would be a reinterpretation of the cephalothin susceptibility disk zone diameters so that it would more adequately predict cefazolin activity.
Trimethoprim Action and Its Analogy with Thymine Starvation
Authors: Amyes S. G. B. , Smith J. T.
Published: June 2012

In a minimal medium, trimethoprim is merely bacteriostatic on the prototroph
Escherichia coli
114. The drug was bactericidal when the amino acids methionine and glycine, plus a purine or purine nucleoside, were also present. This response could be reversed completely when thymine and lysine were added to the culture. Methionine, glycine, and the purine are thought to maintain the integrity of the tetrahydrofolate pool under trimethoprim treatment and prevent the thymidylate synthetase reaction. Thus, the organism behaves phenotypically as a thymineless mutant. The mechanisms by which thymine and lysine reverse the bactericidal effect of trimethoprim in a minimal medium containing methionine, glycine, and adenine is discussed.
Action of a Basic Copolymer of Ornithine and Leucine on Cells of
Staphylococcus aureus
Authors: Shenfeld Avner , Flowers Harold M. , Katchalski Ephraim
Published: June 2012

A basic, random copolymer of
l
-ornithine and
l
-leucine (OL; molar ratios 1:1) was bactericidal to a sensitive (S) strain of
Staphylococcus aureus
at low concentration. Resistant cells (R) were selected from the culture medium and, after serial transfers to solutions containing increasing amounts of the polymer, grew well in the presence of very high concentrations of it (1,000 μg/ml). S cells bound much more OL than did R cells, but no difference in binding was shown between separated cell walls or cell membranes of S and R. The binding of OL and sensitivity to it were not dependent on the teichoic acid-content of the cells. Bound OL was only partially removed from the cells by a variety of reagents, such as sodium dodecyl sulfate, Triton X-100, dilute trichloroacetic acid, and Ba(OH)
2
, and the extent of removal was similar for R and S cells.
Preparation of Succinyl Neocarzinostatin
Authors: Maeda Hiroshi
Published: June 2012

All amino groups in a proteinous antitumor antibiotic, neocarzinostatin, were reacted with succinic anhydride yielding bis-
N
-succinyl neocarzinostatin which retained biological activity in vitro against human cell lines and a bacterium. Amino groups in neocarzinostatin do not appear to play an important role in the activity.
Immunological Responsiveness of Tuberculosis Patients Receiving Rifampin
Authors: Ruben F. L. , Winkelstein A. , Fotiadis I. G.
Published: June 2012

Rifampin has been shown to impair both humoral and cell-mediated immune responses in animal models. In order to detect a similar effect in man, 11 patients with active tuberculosis were evaluated before, 2 weeks after, and 12 to 16 weeks after initiating rifampin. Several parameters were serially measured including blood lymphocytes, intradermal response to intermediate strength tuberculin (PPD), and in vitro proliferative responses to phytohemagglutinin (PHA), a nonspecific mitogen, and to the specific antigens, PPD and influenza A. No changes in lymphocyte counts were noted. No changes in response were noted 2 weeks after beginning treatment with rifampin. However, compared with initial and 2-week responses, the PHA response was reduced by 47%, the PPD by 68%, and the influenza by 75%, and 6 of 11 patients showed no induration after tuberculin skin testing at the 12- to 16-week point. These results indicate that in doses employed for the treatment of tuberculosis, rifampin has an immunosuppressive effect in man that develops gradually.
Comparison of the Distribution of Tobramycin and Gentamicin in Body Fluids of Dogs
Authors: Szwed James J. , Luft Friedrich C. , Black H. R. , Elliott Roger A. , Kleit Stuart A.
Published: June 2012

Tobramycin serum, thoracic lymph, renal lymph, and urine concentrations were measured in mongrel dogs after intravenously administered 5, 10, and 20 mg/kg doses. These were compared with intravenous gentamicin delivered at 5 and 20 mg/kg. Both drugs achieved similar concentrations in serum and thoracic lymph. At 20 mg/kg, tobramycin showed consistently higher renal lymph and urine concentrations than gentamicin. At 5 mg of tobramycin per kg, renal lymph and urine concentrations were higher than with gentamicin only within the 1st h after administration. Thereafter the difference was no longer significant. These data suggest that on the basis of distribution in the body fluids of dogs, tobramycin is a reasonable alternative to gentamicin.
Characterization of a Plasmid Determining Resistance to Erythromycin, Lincomycin, and Vernamycin B
α
in a Strain of
Streptococcus pyogenes
Authors: Clewell Don B. , Franke Arthur E.
Published: June 2012

A plasmid determining resistance to erythromycin, lincomycin, and vernamycin B
α
was isolated from a strain of
Streptococcus pyogenes
. The plasmid has a molecular weight of approximately 17 × 10
6
and is present to the extent of one to two copies per chromosomal genome equivalent.
Detection of an R Factor Showing Temperature-Sensitive Transfer in
Salmonella typhimurium
Isolated from Calves
Authors: Sato Gihei , Kodama Hiroshi , Terakado Nobuyuki
Published: June 2012

An R factor carrying tetracycline resistance, the transfer of which was observed in mating cultures at 25 but not at 37 C, was demonstrated in strains of
Salmonella typhimurium
isolated from calves.
Plasmid-Mediated Production of Staphylococcin in Bacteriophage Type 71
Staphylococcus aureus
Authors: Dajani Adnan S. , Taube Zaiga
Published: June 2012

Staphylococcin production by
Staphylococcus aureus
strain C55 was eliminated when producing strains were exposed to various curing treatments. Acridine orange, ethidium bromide, and sodium dodecyl sulfate each effected less than 15% cure rates in treated cells. Rifampin eliminated the staphylococcin in 83% of treated isolates, and growth at 42 C resulted in a 97% cure rate. Curing of staphylococcin production and elimination of penicillinase plasmid were independent of one another. Several characteristics of the cured strains were examined and compared with the bacteriocin-producing strains. Whereas bacteriocin-producing cells were resistant to the bactericidal action of the staphylococcin and failed to adsorb it, cured cells adsorbed the staphylococcin and were susceptible to its lethal effect.
Multiple Antibiotic Resistance in
Neisseria gonorrhoeae
Authors: Maier Thomas W. , Beilstein Henry R. , Zubrzycki Leonard
Published: June 2012

The sensitivities of gonococcal isolates to six antibiotics were determined for gonococci isolated in Philadelphia in 1972. The degree of association between susceptibilities to any two antibiotics was determined (coefficient of correlation). The correlation between penicillin and tetracycline (r = 0.75) was almost as good as that between two penicillins, penicillin G and ampicillin (r = 0.85), but the difference was statistically significant. The lowest correlation found was between erythromycin and chloramphenicol (r = 0.62), two antibiotics seldom used in gonorrhea therapy. In addition, gonococci most resistant to one antibiotic were the most likely to be multiply resistant. This was found with respect to penicillin, tetracycline, erythromycin, and chloramphenicol. Approximately 40% of gonococci classified as “most resistant” (exceeding the resistance of 75% of all isolates) to one antibiotic were also “most resistant” to three others. Finally, multiply resistant mutants were isolated by selection for resistance to either penicillin or tetracycline. These results provide evidence for the existence of a common mechanism for multiple antibiotic resistance in the gonococcus.
Gentamicin Resistance in
Pseudomonas aeruginosa
: R-Factor-Mediated Resistance
Authors: Bryan L. E. , Shahrabadi M. S. , Van Den Elzen H. M.
Published: June 2012

By disk diffusion antimicrobial susceptibility testing, 11% of 313 consecutive strains of
Pseudomonas aeruginosa
, examined during July to October 1973, were resistant to gentamicin (minimal inhibitory concentration 12.5 to >100 μg/ml), and a further 31% were moderately resistant (6.25 to 12.5 μg/ml) to gentamicin at the University of Alberta Hospital in Edmonton, Canada. Of 45 gentamicin-resistant strains from that hospital, none possessed R-factors or gentamicin-inactivating enzymes. Eight of 13 strains obtained from three American sources, which contained gentamicin-acetylating (12 strains) or -adenylating (1 strain) activity, conjugally transferred both gentamicin resistance and antibiotic-inactivating activity.
P. aeruginosa
recipients were much more effective for detection of transferable gentamicin resistance than
Escherichia coli
recipients, although not all
P. aeruginosa
were equally as effective as recipients. One strain, POW 151, transferred resistance to both carbenicillin and gentamicin as well as to several other antibiotics. R-factors detected belonged to P-2 and P-3 (Com 6, C) incompatibility groups. Expression of gentamicin resistance due to acetylation of gentamicin was subject to marked phenotypic lag, especially in recipient strain
P. aeruginosa
280. This was shown to result in the failure to detect gentamicin resistance transfer if the concentration of gentamicin in selection media was too high (>2.5 μg/ml for strain 280). Some but not all recipients were changed in pyocine type upon acquisition of R-factors.
Microbiological Characterization of Everninomicins B and D
Authors: Sanders W. Eugene , Sanders Christine C.
Published: June 2012

Everninomicins B and D are components of a complex of antibiotic substances produced by
Micromonospora
. Both were shown to be highly active inhibitors of growth of all gram-positive bacteria,
Neisseria
, and
Bacteroides
studied in vitro. Potency of activity appeared to be greater than that of chloramphenicol, but less than that of penicillin G, when assayed against strains susceptible to each of the drugs. The everninomicins were bacteriostatic for all strains tested, except group A streptococci. No facultatively anaerobic gram-negative bacilli were susceptible. Resistant mutants were selected with difficulty from susceptible staphylococci in the laboratory, and these demonstrated no cross-resistance to available antimicrobial agents. Most variations in media, growth conditions, or procedure of assay had little or no effect on antimicrobial activity. Only addition of serum or increase in inoculum size reduced antibacterial activity. Significant differences in activity of the two components were encountered infrequently; the B component was four- to sixfold more active against gonococci and group A streptococci, whereas the D component was fourfold more active against enterococci. Because of the high degree of in vitro activity and lack of resistance among susceptible genera of bacteria, the everninomicins clearly merit further careful study as potential therapeutic agents.
New Antimicrobial Nitrofuran,
trans
-5-Amino-3-[2-(5-Nitro-2-Furyl)Vinyl]-Δ
2
-1,2,4-Oxadiazole: Antimicrobial Efficacy in Mice, Rats, and Guinea pigs
Authors: McRipley R. J. , Gadebusch H. H. , Pansy F. , Semar R.
Published: June 2012

A new antimicrobial nitrofuran designated SQ 18,506 showed some therapeutic activity when administered orally to mice infected with
Escherichia coli, Salmonella schottmuelleri, Shigella flexneri
, or
Klebsiella pneumoniae
. Animals infected parenterally with
Streptococcus pyogenes, Proteus mirabilis, Mycobacterium tuberculosis
, and
Candida albicans
, or topically with
Trichophyton mentagrophytes
, did not respond to therapy with the drug at the dosage levels used. The compound was as effective as metronidazole in the topical treatment of experimental trichomonal infections in mice and in guinea pigs and as effective as nystatin, candicidin, or a sulfanilamide-aminacrine hydrochloride cream in the treatment of a candidal vaginal infection in rats. The chemotherapeutic efficacy of SQ 18,506 in experimental vaginitis caused by
Escherichia coli
in the rat surpassed that shown by four commercial products available for the treatment of bacterial vaginitis.
Treatment of Pneumonia and Other Serious Bacterial Infections with Cephapirin
Authors: Robson Hugh G. , Bowmer M. Ian
Published: June 2012

Nineteen patients with pneumonia due to
Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae
, or
Escherichia coli
were treated with 4 to 18 g of cephapirin daily. There were three treatment failures. One patient each with pneumonia due to
E. coli
or
S. pneumoniae
died despite apparent eradication of the pathogen. Lobar pneumonia due to
K. pneumoniae
progressed during therapy in a third patient to lung gangrene, necessitating pneumonectomy. Five additional patients with pneumococcal pericarditis or septic bursitis, empyema, cannula-associated bacteremia, and thoractomy wound infection due to
S. aureus
were cured. All isolates of
S. aureus, S. pneumoniae
, and group A
Streptococcus
were inhibited by 0.8 μg of cephapirin per ml; minimal inhibitory concentrations of cephalothin were similar. Ninety percent of
K. pneumoniae
, 85% of
Proteus mirabilis
, 73% of
E. coli
, and 30% of
Enterobacter
were inhibited by 12.5 μg cephapirin per ml. All isolates of
Pseudomonas, Serratia
and indole-positive
Proteus
had a cephapirin minimal inhibitory concentration of [Formula: see text] 100 μg/mg. Serum concentrations after intravenous and intramuscular injection were similar to those reported for cephalothin. The intramuscular injections were moderately painful, and intravenous infusions caused phlebitis in three of nine patients treated with doses up to 18 g per day. Cephapirin appears comparable to cephalothin in vitro and is an effective agent in treatment of infection due to
S. aureus
and
S. pneumoniae
.
Effect of Probenecid on the Apparent Volume of Distribution and Elimination of Cloxacillin
Authors: Nauta Ernst H. , Mattie Herman , Goslings Wim R. O.
Published: June 2012

According to Gibaldi et al. (1968, 1970), the higher serum concentrations of penicillins and cephaloridine reached after administration of probenecid are due not only to slower renal elimination but also to an altered distribution in the body. To determine whether probenecid has a direct effect on the distribution of cloxacillin, the elimination and distribution of cloxacillin was studied in six patients, five lacking kidney function and one with a partially impaired renal function, in the presence or absence of probenecid. No significant difference was found between the mean values of the volume of distribution of cloxacillin with and without probenecid (13.0 and 12.6 liters, respectively). Thus, the hypothesis of Gibaldi et al. could not be confirmed for cloxacillin in patients lacking kidney function. In spite of the absence of kidney function, the value of the elimination rate constant was significantly decreased in the presence of probenecid (from 0.326 to 0.263/h). This might be explained by a blockade by probenecid of the elimination of cloxacillin by the liver.
Inhibition of Herpes Simplex Virus Replication by Phosphonoacetic Acid
Authors: Overby L. R. , Robishaw E. E. , Schleicher J. B. , Rueter A. , Shipkowitz N. L. , Mao J. C.-H.
Published: June 2012

Replication of herpes simplex virus in WI-38 cells was inhibited by phosphonoacetic acid, as measured by decreased virus cytopathogenic effect and incorporation of radiolabeled thymidine in virus-infected cells. The drug appeared to have no effect on adsorption, penetration, or release of the virus nor on the synthesis of ribonucleic acid or protein. It appeared to inhibit virus deoxyribonucleic acid synthesis.
Effect of Probenecid on Cerebrospinal Fluid Concentrations of Penicillin and Cephalosporin Derivatives
Authors: Dacey Ralph G. , Sande Merle A.
Published: June 2012

Probenecid may elevate the cerebrospinal fluid (CSF) concentration of penicillin G by inhibiting the excretion of organic acids from CSF. We have studied this phenomenon with various penicillin and cephalosporin derivatives. Penicillin concentrations were determined in rabbits under steady-state conditions before and after intravenous probenecid administration. With both low-dose and high-dose probenecid, CSF penicillin levels increased two to three times as did CSF concentration as a percentage of serum level. The same probenecid effect was consistently demonstrated in animals with experimental pneumococcal meningitis. Probenecid likewise increased the CSF concentration of ampicillin, carbenicillin, nafcillin, cephacatrile, and cefazolin. Probenecid may prove useful in certain bacterial infections where high CSF antibiotic levels are necessary.
Effect of Erythromycin Analogues on Binding of [
14
C]Erythromycin to
Escherichia coli
Ribosomes
Authors: Pestka Sidney , Lemahieu Ronald A.
Published: June 2012

The relative ability of 44 erythromycin analogues to bind to ribosomes was determined by their effect on [
14
C]erythromycin binding to
Escherichia coli
ribosomes. The association and dissociation constants of each of these erythromycin derivatives were determined as well as their interaction coefficient for their binding to ribosomes. Substitutions were made on various portions of the erythromycin molecule with retention of substantial activity as measured by inhibition of [
14
C]erythromycin binding to ribosomes. Since the effect of erythromycin analogues on [
14
C]erythromycin binding to ribosomes provides a relatively sensitive assay for these compounds, erythromycin analogues with relatively little affinity for ribosomes could be detected. Compounds with association constants of 10
4
M
−1
were detectable; the association constant for erythromycin binding to ribosomes was approximately 10
8
M
−1
. Thus, compounds with 0.0001 the association constant of erythromycin were detectable. This assay could be used alone or in conjunction with microbiological assays for primary screening of active analogues or other compounds which interfere with [
14
C]erythromycin binding to ribosomes. It permits an estimate of the general activity of compounds rapidly and directly. Variables such as metabolic modifications of the compounds and permeability are excluded. The present assay reflects the ability of the compounds to interact directly with their target organelle and may serve as a useful adjunct in developing new compounds.
Correlation of Effects of Erythromycin Analogues on Intact Bacteria and on [
14
C]Erythromycin Binding to
Escherichia coli
Ribosomes
Authors: Pestka Sidney , Lemahieu Ronald , Miller Philip
Published: June 2012

The dissociation constants for binding to ribosomes from
Escherichia coli
and concentrations at which 50% inhibition of [
14
C]erythromycin binding to ribosomes occurred were determined for 45 erythromycin analogues. These values were correlated with their antibacterial activities against
Bacillus subtilis
. Compounds which bound to ribosomes best showed the greatest activities; those which were poorly bound to ribosomes showed little or no antibacterial activity. The ribosomal binding assays therefore reflected the general antibacterial potential of the erythromycin analogues.
Isolation and Antibacterial Activity of Acylphloroglucinols from
Myrtus communis
Authors: Rotstein A. , Lifshitz A. , Kashman Y.
Published: June 2012

Isolation procedures of two new acylphloroglucinols, myrtucommulone-A and myrtucommulone-B, from
Myrtus communis
leaves are given. Myrtucommulone-A was highly antibacterial against gram-positive bacteria but was not active against gram negatives. The chemical relation to other acylphloroglucinols and the antibacterial activity of the compounds isolated are discussed.
Biological Activity of Antibiotic G-418, a New
Micromonospora
-Produced Aminoglycoside with Activity Against Protozoa and Helminths
Authors: Waitz J. A. , Sabatelli F. , Menzel F. , Moss E. L.
Published: June 2012

On the basis of parallel in vitro studies with antibiotic G-418, gentamicin, neomycin, and kanamycin, antibiotic G-418 was found to be less potent than gentamicin but more active than either kanamycin or neomycin against most strains, with the exception of
Pseudomonas
, for which neomycin was more active than antibiotic G-418, and enterococci, for which antibiotic G-418 was more active than the other three antibiotics. Mouse protection tests indicated that antibiotic G-418 is approximately half as potent as gentamicin and its acute toxicity is one-half to one-third that of gentamicin.
Interaction of Clindamycin and Gentamicin In Vitro
Authors: Fass Robert J. , Rotilie Carol A. , Prior Richard B.
Published: June 2012

The minimal inhibitory concentrations of clindamycin and gentamicin alone and in combinations were determined by a microdilution method for 163 aerobic, facultative, and anaerobic clinical isolates. All 77 strains of
Staphylococcus aureus, Diplococcus pneumoniae, Streptococcus pyogenes
, and anaerobic bacteria (except for three strains of
Clostridium
) were inhibited by 1.6 μg or less of clindamycin per ml. Gentamicin did not interfere with the activity of clindamycin within the range of concentrations tested (0.1 to 100 μg/ml); for some strains combinations were synergistic. Sixty-two (94%) of 66 strains of
Enterobacteriaceae
and
Pseudomonas aeruginosa
were inhibited by 6.2 μg or less of gentamicin per ml. Combinations of clindamycin and gentamicin were indifferent for 29 strains and synergistic for 33 strains. All 20 strains of enterococcus, three strains of
Clostridium
, three strains of
Escherichia coli
, and one strain of
Proteus rettgeri
were resistant to both clindamycin (minimal inhibitory concentration greater than 3.1 μg/ml) and gentamicin (minimal inhibitory concentration greater than 6.2 μg/ml). Combinations of clindamycin and gentamicin were indifferent for 16 and synergistic for 11 of the resistant strains. Except for clindamycin-sensitive isolates, synergy was usually observed only at concentrations of one or both drugs which are not readily obtainable in vivo. Antagonism was never observed.
Assessment of Cytosine Arabinoside as an Antiviral Agent in Humans
Authors: Lauter Carl B. , Bailey Elizabeth J. , Lerner A. Martin
Published: June 2012

Cytotoxicity, minimal inhibitory concentrations of herpesviruses, and pharmacokinetic studies of cytosine arabinoside (ara-C) were done. Ara-C compared favorably with idoxuridine in in vitro studies of antiviral activity versus herpes simplex, varicella-zoster, and cytomegalovirus. However, ara-C was 10 times more toxic to tissue cultures, and concentrations in serum and urine of three patients who were given ara-C at acceptable dosages (1 mg/kg per day) were not measurable by our assay. These studies predict that ara-C is not likely to be a useful antiviral agent in humans because its therapeutic to toxic ratio approaches unity. These predictions of little clinical efficacy seem now to have been confirmed by clinical trails in humans. Pharmacokinetic studies outlined here should precede and help formulate controlled clinical trials of potential antiviral agents in humans.
Synthesis of Vaccinia Virus Polypeptides in the Presence of Hydroxyurea
Authors: Katz Ehud , Margalith Eva , Winer Bela
Published: June 2012

Hydroxyurea (5 × 10
−3
M) inhibits the development of vaccinia virus in HeLa cells early after infection and prevents the synthesis of viral deoxyribonucleic acid. In the presence of hydroxyurea, late viral polypeptides are not formed, as observed by electrophoresis on polyacrylamide gels.
Interaction of Purulent Material with Antibiotics Used to Treat
Pseudomonas
Infections
Authors: Bryant Richard E. , Hammond Dianne
Published: June 2012

To define factors contributing to the adverse prognosis of patients with gram-negative bacillemia and abscess formation, we studied the interaction between polymyxin B, colistin sulfate, gentamicin, or carbenicillin with purulent material. Carbenicillin activity was not significantly altered by incubation with pus. Equal volumes of antibiotic and purulent sediment decreased the effective concentration of polymyxin B, colistin sulfate, or gentamicin from 100 μg/ml to 3 to 6 μg/ml. One milliliter of purulent sediment bound more than 700 μg of gentamicin and 1,500 μg of polymyxin B or colistin sulfate. This effect occurred rapidly, proceeded at 4 and 37 C, was stable for 24 to 48 h, and was altered, but not abolished, by varying the pH of the solution. Antibiotic activity could be removed from pus by high concentrations of protamine sulfate, heparin, sodium chloride, or potassium chloride, suggesting binding rather than inactivation.
Evaluation of Bis-Benzimidazoles in the Treatment of Murine Lymphocytic Choriomeningitis Virus Infections
Authors: Stella J. P. , Michaelson J. , Dorfman S. L. , Morgan J. H. , Pfau C. J.
Published: June 2012

Seventy percent of the mice receiving (
S,S
)-1,2-bis(5-methoxy-2-benzimidazolyl)-1,2-ethandiol (A36683) in their drinking water lived at least four times longer than control mice when infected with 10 or 100 mean lethal doses of lymphocytic choriomeningitis virus strain UBC. In the next 4 months, most of the survivors died with lymphocytic choriomeningitis-like symptoms. Drug treatment during the first 7 days after infection was found to have no significant effect on virus titers in various organs. The sparing effect of the drug is discussed in terms of immunosuppression.
Chloroquine-Resistant
Plasmodium falciparum
: Effect of Substrate on Chloroquine and Amodiaquin Accumulation
Authors: Fitch Coy D. , Chevli Rekha , Gonzalez Yolanda
Published: June 2012

Glucose stimulates the high-affinity processes of chloroquine and amodiaquin accumulation in owl monkey erythrocytes infected with a chloroquine-susceptible strain of
Plasmodium falciparum
. Although these erythrocytes have greater ability to accumulate amodiaquin than chloroquine, glucose has relatively less effect on amodiaquin accumulation than on chloroquine accumulation. In contrast to these findings with chloroquine-susceptible
P. falciparum
, glucose stimulates amodiaquin but not chloroquine accumulation in erythrocytes infected with chloroquine-resistant
P. falciparum
. This lack of function of a substrate-dependent component of chloroquine accumulation distinguishes chloroquine-resistant from chloroquine-susceptible
P. falciparum
.
Susceptibility of an Insect
Leptomonas
and
Crithidia fasciculata
to Several Established Antitrypanosomatid Agents
Authors: Bacchi C. J. , Lambros C. , Goldberg B. , Hutner S. H. , De Carvalho G. D. F.
Published: June 2012

Growth inhibition of the lower trypanosomatids
Crithidia fasciculata
and a
Leptomonas
from a hemipteron by several established trypanocides and leishmanicides were compared in four complex and one defined media. The
Leptomonas
was more susceptible than
C. fasciculata
in all media, especially to phenanthridines (ethidium, prothidium, isometamidium) and diamidines (pentamidine, diminazene diaceturate [Berenil], hydroxystilbamidine, stilbamidine); concentrations of these drugs required for 50% inhibition of the
Leptomonas
were <5 μg/ml. In contrast,
C. fasciculata
was uninhibited by <20 μg of diamidines per ml and was three- to sixfold less susceptible than the
Leptomonas
to isometamidium and prothidium. Both trypanosomatids were susceptible to nucleoside antibiotics, e.g., nucleocidin. Neither was inhibited by suramin, melarsen, melarsen oxide, or tryparsamide. The
Leptomonas
was more susceptible to standard trypanocides than five other insect trypanosomatids in a complex medium; it was the only one inhibited by <20 μg of stilbamidine and hydroxystilbamidine per ml.
Penicillin: Reversible Inhibition of Forespore Septum Development in
Bacillus megaterium
Cells
Authors: Lawrence Paul J.
Published: June 2012

Benzylpenicillin inhibits the development of the forespore septum in sporulating
Bacillus megaterium
cells. The inhibitory effect is a function of the duration of exposure to the antibiotic and is completely reversible by penicillinase. Under the incubation conditions employed, less than 20% of the covalently bound antibiotic is released from the cells. The penicillin which remains bound to the cells after treatment with penicillinase may be necessary but is not sufficient for the effect; unbound antibiotic in the sporulation medium is also required.
Morphological Alterations of
Pseudomonas aeruginosa
by Ticarcillin: a Scanning Electron Microscope Study
Authors: Prior Richard B. , Warner John F.
Published: June 2012

Pseudomonas aeruginosa
was exposed to 0.1, 1.0, 10, 100, and 1,000 times the minimal inhibitory concentration of ticarcillin in vitro and subsequently examined with the scanning electron microscope. The morphological alterations observed were filamentation, mid-cell defects, and spheroplast formation, and these alterations were dependent upon the drug concentration.
In Vitro Studies with Cephanone
Authors: Shadomy Smith , Kirchoff Carol , Wagner Gerald
Published: June 2012

A new parenteral cephalosporin, cephanone, was studied in vitro.