bluuebunny/crossref_metadata_2025 huggingface dataset:
Cephanone: In Vitro Antibacterial Activity and Pharmacology in Normal Human Volunteers
Authors: Meyers Burt R. , Hirschman Shalom Z. , Nicholas Peter
Published: June 2012

Cephanone, a new 3-heterocyclic-thiomethyl cephalosporin antibiotic, was found to have an antibacterial spectrum similar to that of cephalothin. The compound was active in vitro against a variety of gram-positive and gram-negative bacteria. All strains of
Staphylococcus aureus
tested were inhibited by concentrations of 6.2 μg or less of cephanone per ml. Beta-hemolytic group A streptococci and pneumococci were exquisitely sensitive. Among strains of
Escherichia coli
and
Klebsiella
sp., 83 and 82%, respectively, were inhibited by 3.1 μg or less of cephanone per ml. Excellent serum concentrations of the antibiotic were obtained after parenteral administration. Peak concentrations of 38 and 81.2 μg/ml were achieved in the serum after intramuscular and intravenous doses of 1 g of cephanone, respectively. The serum concentrations of cephanone fell gradually during the 12 hr after administration. Very high concentrations of cephanone were found in the urine.
Comparison of Cefazolin, a New Cephalosporin Antibiotic, with Cephalothin
Authors: Phair John P. , Carleton Judith , Tan James S.
Published: June 2012

Resistance to cephalothin was associated in general with a lack of susceptibility to cefazolin, a new 7-amino cephalosporanic acid derivative.
Locus of Divalent Cation Inhibition of the Bactericidal Action of Polymyxin B
Authors: Chen Chuen-Chin Hsu , Feingold David S.
Published: June 2012

The bactericidal effect of polymyxin B upon two
Pseudomonas aeruginosa
strains and two
Escherichia coli
strains was studied as a function of the concentration of the divalent cations Ca
2+
and Mg
2+
. Lipid spherules in aqueous suspension (liposomes) were prepared from the bacterial phospholipids and were examined for the release of trapped glucose induced by polymyxin B under similar conditions of divalent cation concentration. In contrast to the bacteria, which were protected markedly from the bactericidal action of polymyxin B by Ca
2+
or Mg
2+
at concentrations of 2 × 10
−3
m
or less, neither cation had any protective effect on bacterial liposomes at concentrations up to 2 × 10
−2
m
. These observations suggest that divalent cations antagonize the bactericidal effect of polymyxin B indirectly through interaction with the cell wall rather than at the primary membrane locus of action. The interaction of the divalent cations with the cell wall prevents access of the antibiotic to the cytoplasmic membrane by mechanisms that remain unclear.
Comparison of Mueller-Hinton Agar and Oxoid Sensitivity Test Medium in Antibiotic Susceptibility Testing of
Escherichia coli
Authors: Baker Carol J. , Clark Dorothy J. , Barrett Fred F.
Published: June 2012

The in vitro activity of five antibiotics against 368 strains of
Escherichia coli
was determined by use of Mueller-Hinton agar and Oxoid sensitivity test medium. Minimal inhibiting concentrations were essentially identical with both media.
Antimicrobial effect of beta-lactam antibiotic combinations against Bacteroides fragilis in vitro
Authors: Bansal M B , Thadepalli H
Published: June 2012

Carbenicillin, piperacillin, and mezlocillin, when combined with cefoxitin, exhibited synergism against 20, 13, and 10 isolates of Bacteroides fragilis, respectively, and no antagonism was observed in 19 of 20 strains. These results suggest that if beta-lactamase was induced from B. fragilis by cefoxitin, it was ineffective against the antibiotics tested.
In vitro activities of amphotericin B in combination with four antifungal agents and rifampin against Aspergillus spp
Authors: Hughes C E , Harris C , Moody J A , Peterson L R , Gerding D N
Published: June 2012

Strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger were tested for in vitro susceptibility with a microtiter plate system in buffered yeast-nitrogen base and in buffered minimal essential medium. Isolates were tested against amphotericin B, flucytosine, rifampin, ketoconazole, ICI 153,066, and Bay n 7133 and against combinations of amphotericin B with each of the other five drugs. Combinations of amphotericin B and rifampin were the most active against all three species of Aspergillus. Flucytosine combined with amphotericin B produced little or no reduction of the MICs at which 90% of the strains were inhibited compared with amphotericin B alone. With one exception, the addition of ketoconazole, ICI 153,066, or Bay n 7133 to amphotericin B did not consistently alter the MICs. The addition of ICI 153,066 markedly increased the MICs of amphotericin B against the A. flavus isolates in both media. When the azoles were tested alone, Bay n 7133 was the most active against A. fumigatus, but was two- to fivefold less active against A. flavus. Ketoconazole was the most active azole against A. flavus.
Randomized, double-blind comparison of ceftazidime and moxalactam in complicated urinary tract infections
Authors: Horowitz E A , Preheim L C , Safranek T J , Pugsley M P , Sanders C C , Bittner M J
Published: June 2012

Sixty-seven patients with complicated urinary tract infections were randomized in double-blind fashion to ceftazidime or moxalactam (MOX). A total of 54 patients were evaluable, 27 in each group. Patients received 500 mg of antibiotic intravenously every 12 h, except for those with Pseudomonas aeruginosa randomized to MOX who received 2 g intravenously every 12 h. Toxic effects with ceftazidime were experienced by the following number of patients: pain with infusion, one; posttherapy diarrhea, one; liver function test elevations, two; and neutropenia, one. Toxic effects with MOX were experienced by the following number of patients: liver function test elevations, two; and prolonged prothrombin time, one. All resolved. At 1 week posttherapy, bacteriologic results were 74% cured, 11% relapsed, 15% reinfection with ceftazidime and 52% cured, 33% relapsed, and 19% reinfection with MOX. Ceftazidime was effective for infections caused by MOX-resistant P. aeruginosa. P. aeruginosa resistant to MOX and other beta-lactams was isolated from one patient after MOX therapy. Enterococcal reinfection was common in both groups.
Comparative in vitro antimicrobial activity of carumonam, a new monocyclic beta-lactam
Authors: Smith B R , LeFrock J L , McCloskey R V , Donato J B , Weber S J , Joseph W S
Published: June 2012

The antimicrobial activity of carumonam (formerly RO-17-2301), a monocyclic beta-lactam antibiotic, was compared with those of aztreonam, cefotaxime, cefoperazone, ceftazidime, piperacillin, and gentamicin against 455 bacterial isolates. Carumonam did not possess activity against gram-positive cocci and was generally comparable to aztreonam and ceftazidime for most gram-negative bacilli. However, carumonam was the most active beta-lactam against gentamicin-resistant Pseudomonas aeruginosa strains (90% MIC, 8 micrograms/ml).
Biliary Excretion of a New Semisynthetic Cephalosporin, Cephacetrile
Authors: Brogard J. M. , Haegele P. , Dorner M. , Lavillaureix J.
Published: June 2012

The biliary excretion of a new derivative of cephalosporin, cephacetrile (CIBA 36 278 Ba), was studied (i) in the isolated perfused rabbit liver, (ii) in humans with a duodenal tube, and (iii) in patients after cholecystectomy with a Kehr's drain in the common bile duct. The biliary excretion of the antibiotic was very low in the perfused liver, and no antibiotic activity was found in liver tissue at the end of the experiment. This observation, together with the finding of a rapid decline of the antibiotic concentration in the circulating blood serum, favors the assumption that a metabolic transformation of CIBA 36 278 Ba in liver tissue takes place. In humans, the antibiotic concentration was found to be low both in the duodenal juice and in the bile obtained by external drainage. The biliary concentrations found in these subjects seem to be inferior to those required for the inhibition of the common bacteria of biliary infections. In renal failure, however, the biliary excretion of CIBA 36 278 Ba increased considerably.
Sisomicin: Evaluation In Vitro and Comparison with Gentamicin and Tobramycin
Authors: Crowe Christine C. , Sanders Eugene
Published: June 2012

Sisomicin is a new antibiotic produced by
Micromonospora inyoensis
. The in vitro activities of sisomicin, gentamicin, and tobramycin, three similar aminoglycosides, were determined against 228 clinical isolates representing 10 genera of common pathogens. No difference was noted in the activities of these antimicrobial agents when assayed by a standard broth dilution technique against
Klebsiella, Enterobacter, Escherichia, Salmonella, Citrobacter
, enterococci, or
Staphylococcus aureus
. Sisomicin was significantly more active than tobramycin against
Serratia
and indole-positive
Proteus
strains. Sisomicin was significantly more active than gentamicin against indole-negative
Proteus
strains and slightly more active against indole-positive
Proteus
strains. Tobramycin was more active than sisomicin or gentamicin against
Pseudomonas
and indole-negative
Proteus
strains. Gram-negative bacilli resistant to one of the three antimicrobial agents were not necessarily resistant to either of the other two. Activity of sisomicin was independent of the susceptibility or resistance of these isolates to nine other antimicrobial agents as assayed by the Bauer-Kirby technique. The presence of 50% human serum did not antagonize the in vitro activity of sisomicin against gram-negative isolates. Because sisomicin showed certain advantages over gentamicin or tobramycin in vitro, further investigation of this new antimicrobial agent is warranted.
Effect of Assay Medium on the Antibacterial Activity of Certain Penicillins and Cephalosporins
Authors: Pursiano T. A. , Misiek M. , Leitner F. , Price K. E.
Published: June 2012

It is well known that the composition of the assay medium greatly affects the antimicrobial activity of aminoglycoside antibiotics. A similar response has now been observed with certain penicillins and cephalosporins. In the case of these compounds, this effect is apparently governed by the chemical nature of the penicillin 6- and cephalosporin 7-side chains. In comparison with their activity in Nutrient Broth, the activity of some of the β-lactam antibiotics that have a weakly basic or basic group in their side chain was reduced as much as 40-fold in one or more of the following media: Mueller-Hinton, Trypticase soy, antibiotic assay, and heart infusion broths. In contrast, the assay medium had no effect on the activity of those compounds possessing an acidic or a nonionizable function in their side chain. The extent to which medium influences the antibacterial activity was also dependent upon the assay method and the organism, the effect being more pronounced in broth dilution than in agar dilution tests and occurring more frequently with gram-negative than with gram-positive organisms.
Influence of Methodology upon Apparent Concentrations of Antibiotics in Tissue
Authors: Kaplan J. Martin , McCracken George H. , Snyder Edward
Published: June 2012

This study compares the diffusion in agar of antibiotics prepared in homogenates of tissue, tissue supernatant fluids, whole serum, and buffer solution. Penicillin, erythromycin, cephalothin, gentamicin, and colistin sulfate were studied. With the exception of erythromycin in supernatant fluid of human tonsil, zones of inhibition in agar were consistently smaller in homogenate and supernatant fractions of tissue than in serum and buffer. Thus, a significant error of underestimation occurred when a buffer standard curve was used for assaying antimicrobial activity in homogenates of tissue. This error ranged from 23 to 66% in 10% guinea pig liver homogenate and from 43 to 78% in 20% liver homogenate. A similar, but smaller error of under-estimation resulted with supernatant fractions of tissue except with erythromycin, for which a 25 to 56% error of overestimation occurred when activity in supernatant fraction of tonsil was read off a buffer standard curve. These results emphasize the importance of preparing the standard antibiotic curve with material having agar diffusion properties similar to those of the material being assayed.
Bactericidal Action of Sulfhydryl Binding Compounds
Authors: Tuli V.
Published: June 2012

An oxidation product of indole-3-acetic acid, 3-methyleneoxindole, is highly reactive with free sulfhydryl groups. It has been shown to be a potent bactericidal agent in actively growing cultures. The bactericidal action of 3-methyleneoxindole was found to be independent of protein or deoxyribonucleic acid synthesis but to require the capacity for ribonucleic acid synthesis. The reactions underlying the bactericidal effect of 3-methyleneoxindole are not unique to it among compounds which can bind free SH groups, since
N
-ethylmaleimide appeared to have a similar mode of action.
Drug Resistance of Coliform Bacteria in Hospital and City Sewage
Authors: Grabow W. O. K. , Prozesky O. W.
Published: June 2012

The number and properties of drug-resistant coliform bacteria in hospital and city sewage were compared. There was little difference in the counts of organisms with nontransferable resistance to one or more of 13 commonly used drugs. An average of 26% of coliforms in hospital waste water had transferable resistance to at least one of the drugs ampicillin, chloramphenicol, streptomycin, sulfonamide, or tetracycline as compared to an average of 4% in city sewage. R
+
bacteria in the hospital discharge were also resistant to a broader spectrum of drugs than those in city sewage. In both effluents, the occurrence of fecal
Escherichia coli
among R
+
coliforms was twice as high as among coliforms with nontransferable resistance. Resistance was transferable to
Salmonella typhi
, and such drug-resistant pathogens in the water environment could be of particular concern. The significance of the results with regard to environmental pollution with R
+
bacteria and the dissemination of these organisms is discussed.
Effect of 1-β-
d
-Ribofuranosyl-1,2,4-Triazole-3-Carboxamide (Virazole, ICN 1229) on Herpes and Vaccinia Keratitis and Encephalitis in Laboratory Animals
Authors: Sidwell Robert W. , Allen Lois B. , Khare G. P. , Huffman John H. , Witkowski J. T. , Simon Lionel N. , Robins Roland K.
Published: June 2012

Topical application of 1-β-
d
-ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole) significantly inhibited the development of herpetic keratitis in the eyes of rabbits, as determined by both infectivity and Draize scoring parameters. Significant inhibition of the infection was demonstrated with 10% concentrations of Virazole; a 1% solution had a moderate effect, whereas doses of 0.1 and 0.01% had little activity in this system. A 5% concentration of Virazole similarly inhibited vaccinia keratitis in rabbits. Encephalitis-induced mortality in hamsters initially infected intraocularly with herpesvirus was significantly prevented or inhibited by topical application of 5, 10, and 20% concentrations of Virazole. Surviving, treated hamsters had no signs of herpes keratitis. The 20% concentration was the approximate LD
50
in hamsters. Virazole administered subcutaneously or intraperitoneally to mice did not appreciably alter the course of herpes virus- or vaccinia virus-induced encephalitis in these animals, although in a herpesvirus experiment direct injection of the drug into the brains 3 hr prior to virus inoculation resulted in a significant survivor increase.
Double-Blind Controlled Comparison of Phlebitis Produced by Cephapirin and Cephalothin
Authors: Carrizosa Jaime , Levison Matthew E. , Kaye Donald
Published: June 2012

In a double-blind study with each patient as his own control cephapirin and cephalothin were administered to 20 patients in opposite arms for a period of 48 hr each. Neither the incidence of phlebitis nor the degree of phlebitis was significantly different with the two drugs, and there was no difference in the time of onset of pain or phlebitis.
Discrepancy Between Carbenicillin and Ampicillin Activities Against Enterococci and
Listeria
Authors: McCracken George H. , Nelson John D. , Thomas Marion L.
Published: June 2012

For infections of the newborn, carbenicillin has theoretical advantages over ampicillin, when given with an aminoglycoside, because of its activity against
Pseudomonas
and many indole-positive
Proteus
strains. Agar and broth dilution susceptibility studies demonstrated comparable activities of carbenicillin and ampicillin against coliform organisms but greater resistance of enterococci and
Listeria
to carbenicillin. However, the significance of the higher inhibitory concentrations is questionable because many serum specimens containing concentrations of carbenicillin lower than the minimal bactericidal values for
Listeria
and enterococcus strains had demonstrable in vitro bactericidal activity. Carbenicillin and gentamicin combinations had greater antibacterial activities than either drug alone against all enterococci tested and against 50% of
Listeria
strains. The questions of efficacy raised by contradictory in vitro data may be answered by clinical studies of carbenicillin and gentamicin in infections of the newborn.
Turbidimetric Bioassay for Carbenicillin
Authors: Stankewich Joseph P. , Upton Ronald P.
Published: June 2012

A quantitative turbidimetric bioassay has been developed for carbenicillin with the use of a strain of
Escherichia coli
. The assay is relatively specific for carbenicillin and is not affected by 10% (wt/wt) benzylpenicillin. It has been demonstrated to be more precise than the plate diffusion assay. Since it is readily automated, it is also faster and less expensive. The influence of pH, time, and extent of growth on the assay has been evaluated.
Cephalosporinase Activity in
Bacteroides fragilis
Authors: Bene Victor E. Del , Farrar W. Edmund
Published: June 2012

Cephalosporinase activity was demonstrated in all of 10 strains of
Bacteroides fragilis
investigated. Low rates of hydrolysis of cephalosporins (0.25 to 3.5 μmol of cephaloridine per h per 10
9
cells) were found, but no activity against penicillin substrates was detected. In two strains the cephalosporinase activity was increased 40-and 80-fold by growing cells in the presence of penicillin. No permeability barrier for these antibiotics was demonstrated. In most cases the substrate profile showed decreasing activity in the following order: cephaloridine > cephalothin > cephaloglycin > cephalexin. The cephalosporinase from these organisms differed from that found in facultative and aerobic gram-negative bacilli in that it was inhibited by both cloxacillin and
p
-chloromercuribenzoate. Among nine strains of
Bacteroides fragilis
subspecies
fragilis
, correlation was found between in vitro resistance to cephaloridine and amount of β-lactamase activity in sonically disrupted cells.
Chemotherapeutic Activity of Combination Doses of Chloroquine, Pyrimethamine, and Sulfamethoxy-diazine, a Long-Acting Sulfanilamide, Against
Plasmodium berghei
Infections in Mice
Authors: Berberian Dicran A. , Slighter Ralph G.
Published: June 2012

During the course of antimalarial screening, it was discovered that sulfamethoxydiazine, a long-acting sulfanilamide extensively used in genitourinary tract infections, not only was effective against
Plasmodium berghei
infections in mice when administered alone but also was active when used in combination with chloroquine, in effect making it possible to use half as much of the latter drug as normally required to achieve the same results. The triple combination of chloroquine, sulfamethoxydiazine, and pyrimethamine, when administered in a ratio of 30:10:1, was found to be potentiating against both blood-induced and sporozoite-induced
P. berghei
NK
65
infections. Mean effective dose values were calculated for chloroquine, sulfamethoxydiazine, and pyrimethamine against blood-induced
P. berghei
infection, and when a combination of the three drugs was administered therapeutically in the ratio given above, only one-tenth as much chloroquine, one-thirtieth as much sulfamethoxydiazine, and one-sixtieth as much pyrimethamine were needed to cure 50% of murine infections as was needed for each drug alone. The triple combination also showed enhanced activity against lethal sporozoite-induced
P. berghei
NK
65
infection in A/J strain mice.
Metabolism of Penicillins to Penicilloic Acids and 6-Aminopenicillanic Acid in Man and Its Significance in Assessing Penicillin Absorption
Authors: Cole M. , Kenig M. D. , Hewitt Valerie A.
Published: June 2012

Penicillins can be metabolized to penicilloic acids in man, the extent being dependent on the penicillin structure. In the phenoxy penicillin series, phenoxymethyl penicillin was found to be particularly unstable, but the higher homologues were more stable. In the isoxazolyl series, oxacillin was unstable, and progressive insertion of halogen in the phenyl ring increased stability. Ampicillin and amoxycillin showed some instability, ampicillin possibly being the more stable. After intramuscular administration, carbenicillin was very stable in the body, ampicillin was fairly stable, and benzyl penicillin was unstable. It is important to take into account the penicilloic acid content of urine when estimating total absorption of a penicillin. Increased stability in the body as well as slower renal clearance can lead to high concentrations in the serum. Penicilloic acids seemed to be more slowly cleared from the body than penicillins. The liver is probably the site of inactivation.
Demonstration of R Factors in
Bordetella bronchiseptica
Isolated from Pigs
Authors: Terakado Nobuyuki , Azechi Hayami , Ninomiya Kiyoji , Shimizu Takeshi
Published: June 2012

Transferability of drug resistance in strains of
Bordetella bronchiseptica
isolated from pigs was examined. These strains were resistant to sulfadimethoxine (SA, more than 1,600 μg/ml), streptomycin (SM, more than 800 μg/ml), and aminobenzyl penicillin (APC, 200 μg/ml). All of them could transfer their drug resistance as one unit to a sensitive strain of
Escherichia coli
as well as to
B. bronchiseptica
by mixed cultivation. The transferred SM-SA-APC resistance in the exconjugants of
E. coli
and
B. bronchiseptica
was also transmissible by mixed cultivation. But the transfer of triple resistance was not mediated by the cell-free filtrate of the drug-resistant strain of
B. bronchiseptica
which was used as donor. The triple resistance in the exconjugant
E. coli
ML1410 was found to be eliminated as a whole by treatment with acriflavin. According to these results, it could be safely concluded that R factors carrying SM-SA-APC resistance were demonstrated in strains of
B. bronchiseptica
isolated from pigs.
Studies on the Action of Nalidixic Acid in the Yeast
Saccharomyces cerevisiae
Authors: Michels C. A. , Blamire J. , Goldfinger B. , Marmur J.
Published: June 2012

The effect of the antibiotic nalidixic acid on macromolecular metabolism in the yeast
Saccharomyces cerevisiae
has been studied. It was found that, upon the addition of nalidixic acid to a logarithmically growing culture, there is a transient inhibition of total cell ribonucleic acid, deoxyribonucleic acid, and protein synthesis, after which the cells show an almost complete recovery. In addition, there is no preferential inhibition of yeast mitochondrial deoxyribonucleic acid synthesis.
Sex Pili Mutants Isolated by Macarbomycin Treatment
Authors: Iyobe S. , Mitsuhashi S. , Saito T.
Published: June 2012

Macarbomycin (MM) preferentially kills
Escherichia coli
carrying episomes derepressed for sex pili formation (
drd
episomes). Using MM, we have isolated various types of mutants from both F-
lac.tet
and R100-1 episomes and have classified them into two types by sex pili formation. Among 26 mutants, 20 could not produce pili and had lost both the ability for conjugal transmission and sensitivity to male phages. From 12 of these 20 mutants, revertants capable of pili formation could be obtained. Most of these had simultaneously regained susceptibility to MM, indicating that the MM susceptibility of
E. coli
carrying
drd
episomes is due to pili formation. Three of the revertants could not confer MM susceptibility on their host and two of them could not produce normal pili, indicating that there are some types of pili insensitive to MM. The six MM-resistant mutants could produce pili, but the frequency of pili formation was slightly lower than that of their parent episomes. Mutants of this type exhibited various degrees of decrease in conjugal transferability or male phage sensitivity, and one mutant produced pili that were altered in shape. It is suggested that this latter mutant became MM-resistant as a result of changes in the chemical composition of its pili.
Curing of an R Factor from
Escherichia coli
by Trimethoprim
Authors: Pinney R. J. , Smith J. T.
Published: June 2012

R factor 1818, which we have shown previously to be eliminated by thymine starvation, was cured from three strains of
Escherichia coli
K-12 by overnight exposure to trimethoprim. Elimination was abolished in the presence of added thymine or thymidine, which suggests that curing is the result of the induction of thymineless conditions by trimethoprim. Starvation of the required amino acids proline and histidine had little effect on elimination, whereas methionine deprivation enhanced it. R factor curing was abolished by the presence of chloramphenicol, and it is concluded that protein synthesis is required for elimination to occur. It is suggested that elimination may result from the activity of a nuclease which is synthesized or induced during both direct thymine starvation and by trimethoprim treatment.
Lomofungin, an Inhibitor of Deoxyribonucleic Acid-Dependent Ribonucleic Acid Polymerases
Authors: Cano F. R. , Kuo S.-C. , Lampen J. O.
Published: June 2012

Lomofungin, an antibiotic active against fungi, yeasts, and bacteria, was found to be a potent inhibitor of purified
Escherichia coli
deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase. It prevents RNA synthesis by a direct interaction with the polymerase and not with the template or substrate; chain elongation is halted promptly. Three DNA-dependent RNA polymerases isolated from
Saccharomyces
strain 1016 were also sensitive to the antibiotic. Lomofungin does not appear to react generally with proteins, as bovine serum albumin did not prevent the inhibitory effect and numerous other enzymes were not affected by lomofungin.
Microbiological Assay for Estimating Concentrations of
dl
-Alanosine in Mouse Tissue
Authors: Pittillo Robert F. , Woolley Carolyn
Published: June 2012

A sensitive, precise microbiological assay was developed for the determination of tissue distribution of
dl
-alanosine, a new antitumor agent.
Safety and efficacy of topical norfloxacin versus tobramycin in the treatment of external ocular infections
Authors: Jacobson J A , Call N B , Kasworm E M , Dirks M S , Turner R B
Published: June 2012

Bacterial conjunctivitis appears to resolve more rapidly when treated with appropriate topical antimicrobial agents. In this multicenter, randomized, double-blind study of efficacy and safety, patients with presumed bacterial external eye infections were assigned to topical therapy with 0.3% norfloxacin or 0.3% tobramycin. A total of 120 patients were enrolled. Of the total, 65 had documented bacterial infections and were evaluable; 59 of these patients had bacterial conjunctivitis. All of the patients with documented infections were cured or improved regardless of the drug treatment regimen or in vitro susceptibility testing results. The most common bacteria isolated were Haemophilus influenzae, Streptococcus pneumoniae, alpha-hemolytic streptococci, Staphylococcus aureus, and Staphylococcus sp. No patients had serious adverse reactions attributed to their therapy. Norfloxacin ophthalmic solution seems to be a safe, effective, and appropriate agent for the treatment of bacterial external eye infections.
In vitro activity of CP-65,207, a new penem antimicrobial agent, in comparison with those of other agents
Authors: Gootz T , Retsema J , Girard A , Hamanaka E , Anderson M , Sokolowski S
Published: June 2012

CP-65,207 is a new parenteral penem antibiotic with a broad spectrum that includes gram-positive, gram-negative, and anaerobic microorganisms, with MICs for 90% (MIC90s) of the majority of 1,101 clinical pathogens tested being less than or equal to 1 microgram/ml. The compound was from 10- to 100-fold more active than cefoxitin and broad-spectrum cephalosporins against gram-positive bacteria and anaerobes. CP-65,207 was less active than imipenem for staphylococci, group A streptococci, and Enterococcus faecalis. Against members of the family Enterobacteriaceae, CP-65,207 was in general 100-fold more active than cefoxitin, 5- to 10-fold more active than broad-spectrum cephalosporins, and 2-fold more active than imipenem. Fresh clinical isolates that were resistant to broad-spectrum cephalosporins were highly susceptible to CP-65,207 and imipenem (MIC90, 1 microgram/ml). Isolates of Enterococcus faecalis, Serratia marcescens, and anaerobic Peptococcus spp. had MIC90s of 8, 2, and 3.12 micrograms/ml, respectively. CP-65,207 was not very active against methicillin-resistant staphylococci or Pseudomonas aeruginosa. Killing kinetics showed that against some strains CP-65,207 is rapidly bactericidal at concentrations well below those required to achieve a similar degree of killing with cefotaxime, ceftazidime, and ceftriaxone. CP-65,207 was only slightly susceptible to hydrolysis by type I cephalosporinases and TEM-1, SHV-1, and PSE-2 plasmid-encoded enzymes. It had the highest affinity for penicillin-binding proteins 2, 1A, 1B, and 3 in cell-free preparations of Escherichia coli W-7.
Comparative in vitro activity of WIN 57273, a new fluoroquinolone antimicrobial agent
Authors: Eliopoulos G M , Klimm K , Rice L B , Ferraro M J , Moellering R C
Published: June 2012

The in vitro activity of WIN 57273, a new fluoroquinolone antimicrobial agent, was evaluated against approximately 600 bacterial isolates. The new drug was 4- to 128-fold more active than ciprofloxacin against a broad range of gram-positive organisms, with the new drug inhibiting 90% of strains of each species except Enterococcus faecium at concentrations of less than or equal to 0.25 microgram/ml. WIN 57273 was four- to eightfold less active than ciprofloxacin against many members of the family Enterobacteriaceae, but the MICs of the new drug for 90% of strains tested (MIC90s) were less than or equal to 8 micrograms/ml (range, 0.25 to 8 micrograms/ml) for all species. Branhamella catarrhalis, Haemophilus influenzae, Neisseria gonorrhoeae, and Legionella spp. were highly susceptible (MIC90s, less than or equal to 0.06 microgram/ml). WIN 57273 demonstrated excellent activity against anaerobes (MIC90s, less than or equal to 0.25 microgram/ml), and the drug was also more active than ciprofloxacin against 30 strains of Mycobacterium avium-M. intracellulare (MIC, 0.1 to 1.0 microgram/ml). The activity of WIN 57273 against gram-positive organisms was minimally affected by pH and increased at low pH (5.4) against gram-negative organisms. The bactericidal activity of WIN 57273 was demonstrated by time-kill techniques against selected organisms. The frequencies of spontaneous resistance to the new agent were low, but resistant colonies could be selected after serial passage of initially susceptible organisms through incremental concentrations of the drug.
Safety of fleroxacin coadministered with theophylline to young and elderly volunteers
Authors: Parent M , St-Laurent M , LeBel M
Published: June 2012

The influence of multiple doses of fleroxacin on the plasma clearance and the urinary excretion of theophylline was studied in 19 young and 18 elderly male volunteers. A theophylline dosage individualized to obtain a mean theophylline concentration in plasma of 10 +/- 3 micrograms/ml was administered for 1 week to each subject. At week 2, oral fleroxacin (400 mg once daily) was added. Theophylline concentrations in plasma were measured with TDx (Abbott Diagnostics, Mississauga, Ontario, Canada), and urinary excretion of theophylline and its three major metabolites was measured by high-performance liquid chromatography. Total theophylline clearance remained essentially unchanged throughout the study period (3.5 and 2.9 liters/h in the young and the elderly, respectively) both after a single fleroxacin dose and after multiple doses. Although significant changes occurred in the urinary excretion of unchanged theophylline and its metabolites after a single fleroxacin dose, no changes were observed after multiple doses. Side effects consisted mainly of gastrointestinal and sleep disturbances, more related to theophylline; photosensitivity was observed in six subjects and was attributed to fleroxacin. We conclude that fleroxacin may be administered concomitantly with theophylline in either young or elderly patients. Close monitoring of theophylline concentrations in serum should be performed, particularly in patients with chronic obstructive pulmonary disease, for whom data are currently lacking.
In vitro susceptibility of Xanthomonas (Pseudomonas) maltophilia to newer antimicrobial agents
Authors: Khardori N , Reuben A , Rosenbaum B , Rolston K , Bodey G P
Published: June 2012

The susceptibilities of 45 clinical and 3 environmental isolates of Xanthomonas maltophilia to 14 antimicrobial agents was determined by broth microdilution. The newer quinolones PD117596, PD117558, PD127391, A-56620, amifloxacin, and fleroxacin were the most active agents tested, with 70 to 99% of isolates being susceptible to these agents. All isolates were resistant to trospectomycin. The new aminoglycosides SCH24120 and SCH22591 were active against 12 and 1% of isolates, respectively.
Amelioration of zidovudine-induced fetal toxicity in pregnant mice
Authors: Gogu S R , Beckman B S , Agrawal K C
Published: June 2012

The effects of zidovudine (AZT) on the fetus were investigated in pregnant mice by using parameters such as the number of fetuses, fetal size, and the fetal hepatic cell clonogenic assay. AZT caused dose-dependent toxicity to the fetus upon administration via drinking water to pregnant mice from days 1 to 13 of gestation. At the 0.5-mg/ml dose level, AZT caused a decrease in the number of fetuses to 12 from an average of 16.5 in control animals, and the fetal size (crown-rump length) was reduced from 10.5 to 8.5 mm. The CFU of the erythroid progenitor cell colonies derived from the fetal hepatic cells were decreased to 38% of that of the control, and the hematocrit dropped to 33.5 +/- 1.7 from a control value of 42.6 +/- 2.5. Concomitant administration of erythropoietin, vitamin E, or interleukin-3 to the AZT-treated pregnant mice caused a significant reversal in the AZT-induced toxicity to the fetus and to the mother's bone marrow. The success of therapeutic intervention was demonstrated by (i) restoration of the number of fetuses to the level of untreated controls, (ii) an increase in the size of fetuses to normal values, and (iii) an increase in hematocrit to > 40. The results suggest that AZT is toxic to the fetus in a dose-dependent manner and that treatment with erythropoietin, vitamin E, or interleukin-3 can ameliorate the AZT-induced fetal toxicity.
Use of fluoroquinolones for prophylaxis of murine Pneumocystis carinii pneumonia
Authors: Brun-Pascaud M , Fay M , Zhong M , Bauchet J , Dux-Guyot A , Pocidalo J J
Published: June 2012

We compared the prophylactic activities of six fluoroquinolones against Pneumocystis carinii pneumonia in immunosuppressed rats. Pefloxacin was the only agent which was as effective as the reference drug trimethoprim-sulfamethoxazole. Clinical trials with pefloxacin in patients at risk for P. carinii pneumonia appear to be justified.
In vitro activity of biapenem (L-627), a new carbapenem, against anaerobes
Authors: Aldridge K E , Morice N , Schiro D D
Published: June 2012

We tested 441 clinical strains of anaerobes by using a broth microdilution method to determine the in vitro activity of biapenem for comparison with those of other agents. Biapenem had activity comparable to those of imipenem and meropenem against all groups of anaerobes with MICs for 90% of the strains tested of 0.06 to 2 micrograms/ml. Against the Bacteroides fragilis group, biapenem was more active than ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin, cefoxitin, cefotaxime, and ceftriaxone. Biapenem was also active against all of the B. capillosus, Prevotella, Clostridium, and Eubacterium strains and anaerobic cocci tested. Against all of the anaerobes tested, biapenem was 32- and 4-fold more active than clindamycin and metronidazole, respectively. These data indicate broad-spectrum activity by biapenem against anaerobes.
Culture microtitration: a sensitive method for quantifying Leishmania infantum in tissues of infected mice
Authors: Buffet P A , Sulahian A , Garin Y J , Nassar N , Derouin F
Published: June 2012

We developed a microtitration method to determine the parasite burdens in homogenized organs of mice infected with Leishmania infantum. This method proved more sensitive than direct enumeration of amastigotes in stained organs, was appropriate for describing the kinetics of infection, and can be considered for physiopathological or pharmaceutical experimental studies.
Separation and Detection of Tetracyclines by High-Speed Liquid Chromatography
Authors: Butterfield A. G. , Hughes D. W. , Pound N. J. , Wilson W. L.
Published: June 2012

The high-speed liquid chromatographic behavior of 15 tetracyclines on anion- and cation-exchange columns is described and illustrated by typical separations of a number of tetracycline derivatives on several systems, as well as by the resolution of tetracycline from its degradation products epi-, epianhydro-, and anhydrotetracycline. These serve as a basis for a rapid, convenient, and precise method for the direct detection of the tetracycline antibiotics and their degradation products.
Synthesis of Vaccinia Virus Polypeptides in the Presence of Isatin-β-Thiosemicarbazone
Authors: Katz Ehud , Margalith Eva , Winer Bela , Goldblum Natan
Published: June 2012

Isatin-β-thiosemicarbazone (IBT) at a concentration of 14 μM inhibited the multiplication of vaccinia virus in HeLa cells. For the first 3 h after infection, viral deoxyribonucleic acid (DNA) was synthesized in the presence of IBT at the same rate as in the control culture; the replication rate declined at a later stage. The DNA failed to be coated with proteins and to become resistant to deoxyribonuclease unless IBT was removed. “Early” and “late” viral polypeptides were formed in the presence of IBT, as revealed by polyacrylamide gel electrophoresis. The formation from precursor of a core polypeptide, a reaction blocked by rifampin, was not affected by IBT. Therefore, it is suggested that a maturation step later than the one blocked by rifampin is involved in the inhibition of vaccinia virus by IBT.
Utilization of Carbon and Nitrogen Sources by
Streptomyces kanamyceticus
for Kanamycin Production
Authors: Basak Ketaki , Majumdar S. K.
Published: June 2012

To select a suitable synthetic medium for kanamycin production, we tested a number of carbon and nitrogen compounds for their effect on growth of
Streptomyces kanamyceticus
ATCC 12853 as well on kanamycin production. Galactose was found to be the most suitable carbon source, though dextrin, soluble starch, and potato starch gave moderate yields. Sodium nitrate and glycine were adequate nitrogen sources for kanamycin production. There was, however, no direct relation between the growth of the organism and antibiotic formation. The pH of the medium might be an important factor for kanamycin formation, as media giving high kanamycin yields showed an alkaline pH without exception.
Inhibition of Granulocyte-Macrophage Colony Formation In Vitro by Substituted Isatin Thiosemicarbazones
Authors: McNeill T. A.
Published: June 2012

The 1-methylisatin derivative of isatin thiosemicarbazone was previously shown to inhibit granulocyte-macrophage colony growth in vitro by an action at the early stages of colony development. The parent compound isatin thiosemicarbazone and 25 other derivatives were tested, and a wide range of activity was found (50% colony inhibition from 0.07 to > 100 μg per ml of culture). High activity was not associated with any specific substituent although 1-methyl or 1-ethyl isatin groups in association with 4′4′ morpholino or 4′4′ tetramethylene thiosemicarbazone substitutions were within the most active group. No correlation between the antimarrow and known antiviral activities of these compounds was apparent. Two of the more active compounds were compared with methisazone and were shown to have the same property of selective action on the early stages of granulocyte-macrophage differentiation in culture. It is suggested that this group of compounds might possibly provide some useful antileukemia agents.
Isolation and Purification of Antibiotic Material from
Physarum gyrosum
Authors: Schroeder H. R. , Mallette M. F.
Published: June 2012

The myxomycete
Physarum gyrosum
was cultured in its plasmodial stage on agar plates containing 0.025 M phosphate buffer at pH 6.5, 2% bakers' yeast, and 0.2% glucose and was supplemented with live
Escherichia coli
. Extracts of these plasmodia contained several antibiotic substances. Antibiotic materials were partially purified by dialysis of the agar medium-mold mixture, evaporation of the dialyzate, and butanol extraction of the residue. Further purification in two paper and two thin-layer chromatographic systems gave one product which was pure in six thin-layer chromatographic systems. Antibiotic activity against some gram-positive and gram-negative bacteria and yeasts was demonstrated with partially purified extracts and a paper-chromatographically separated fraction. One pure antibiotic was effective against
Bacillus cereus
.
Drug-Resistant
Escherichia coli
and
Klebsiella-Enterobacter
in Healthy Adults in Thailand and the Effect of Antibiotic Administration
Authors: Koonkhamlert Chawewan , Sawyer William D.
Published: June 2012

Antibiotic-resistant strains of
Escherichia coli
and, to a lesser extent,
Klebsiella-Enterobacter
were common in serial samples of the normal intestinal flora of healthy young adults in Thailand, and the resistance often was to multiple drugs and was transferable. Antibiotic administration promoted dominance of the flora by drug-resistant organisms regardless of the drug regimen and the predrug susceptibility pattern of the flora. The normal pattern was regained slowly after the cessation of drug administration.
Serum Antibiotic Concentrations Pre- and Postcardiopulmonary Bypass
Authors: Kluge Ronica M. , Calia Frank M. , McLaughlin Joseph S. , Hornick Richard B.
Published: June 2012

Serum concentrations of cephalothin or kanamycin, or both, were determined in 53 patients undergoing cardiopulmonary bypass. Conventional doses of these antibiotics did not provide serum levels above the accepted minimum inhibitory concentrations in children. Adults had adequate serum antibiotic concentrations only when the antimicrobials were administered within 4 h of beginning cardiopulmonary bypass. The impact of these variations upon the occurrence of infectious endocarditis could not be appraised since no cases of infective endocarditis were seen during a 4-month postoperative period.
Regulation of the Bacterial Cell Wall: Effect of Antibiotics on Lipid Biosynthesis
Authors: Hebeler Bruce H. , Chatterjee Anadi N. , Young Frank E.
Published: June 2012

Antibiotics that inhibit the biosynthesis of the cell wall, such as vancomycin, penicillin,
d
-cycloserine, and bacitracin, stimulate the incorporation of lysine into lipids that are extractable with
n
-butanol-6 M pyridinium acetate. Approximately 93% of this lysine is in lysylphosphatidylglycerol (LPG). The remaining lysine is incorporated in another as yet uncharacterized lipid. Because the lysine in the latter lipid is released by mild alkaline hydrolysis, it is not the C
55
-isoprenyl-pyrophospho-
N
-acetyl-muramyl pentapeptide. Vancomycin and penicillin stimulate the incorporation of lysine into both LPG and the minor lipid fractions, whereas treatment with
d
-cycloserine results in an increase only in LPG. Antibiotics that inhibit protein synthesis do not influence the incorporation of lysine into the lipid fractions. Analysis of the extracted lipids indicate that the incorporation of radioactive lysine into LPG is due to an enhancement in synthesis of LPG from phospholipids in the cytoplasmic membrane.
Serum and Urinary Concentrations of Cyclacillin in Humans
Authors: Hertz C. G.
Published: June 2012

Cyclacillin is a semisynthetic penicillin produced from the penicillin nucleus (6-aminopenicillanic acid) by acylation with 1-aminohexanecarboxylic acid. The absorption and excretion characteristics of cyclacillin were defined in one completely randomized and three three-way crossover experiments. Mean peak serum cyclacillin levels appeared earlier and were fivefold higher than those obtained with equal doses of ampicillin. High serum cyclacillin concentrations were reached at 0.5 h and by 2 h were lower than ampicillin. Serum ampicillin concentrations peaked at 1.5 h, remaining slightly higher than those for cyclacillin for the next 4.5 h. The mean area for the cyclacillin curve was significantly superior to either of the ampicillin formulations. Mean serum concentrations of cyclacillin exhibited a smooth dose-response, approximately doubling in each instance as the dose was doubled from 250 to 500 and from 500 to 1,000 mg. High concentrations of cyclacillin were also demonstrated in urine. Neither ratio of drug to metabolite in the urine nor the percent of excretion was significantly affected by the dose level. Sixty-seven percent of the drug was excreted unchanged, and 17% was excreted as penicilloic acid, with most of the excretion occurring within 6 h of administration. In subjects given 500 mg of cyclacillin (four times daily) for 6 days, 2% of the drug was excreted as 1-aminocyclohexanecarboxylic acid, and approximately 55% (24 to 91%) was unchanged. Neither formation nor excretion of the former was sex dependent.
Differences in the Growth of
Aspergillus fumigatus
on Cycloheximide Media at Three Temperatures
Authors: Berger Carole L. , Merz W. G. , Silva-Hutner Margarita
Published: June 2012

Cycloheximide (up to 0.4 g/liter) was significantly more inhibitory to the growth of three isolates of
Aspergillus fumigatus
at 23 C than at 37 or 45 C. Preincubation of the media for 7 days at 45 C did not alter the inhibitory effect of the cycloheximide at 23 C. Neither mutation nor adaptation in the fungus seems to be the reason for its growth on the antibiotic at the higher temperature. The mechanism for the differences in sensitivity as related to temperature of incubation cannot be explained at this time.
Bactericidal Activity and Pharmacology of Cefazolin
Authors: Bergeron Michel G. , Brusch John L. , Barza Michael , Weinstein Louis
Published: June 2012

The in vitro bactericidal activity of cefazolin was found to be similar to that of cephaloridine and cephalothin but slightly greater than that of cephalexin against a majority of 233 strains of gram-positive and gram-negative organisms. Cefazolin, however, was two- to eightfold more active than the other two drugs against
Escherichia coli
and klebsiella. The mean peak concentrations in the serum in 10 normal subjects 1 h after intramuscular injections of 1,000, 500, and 250 mg of cefazolin were 38.8, 18.6, and 12.2 μg/ml, respectively. The antibiotic could still be detected at 8 h. Peak values for a given dose of cephaloridine were comparable. However, blood levels of cefazolin were regularly higher than those of cephaloridine over the first 8 h. The mean half-life of cefazolin in the serum was 2 h, whereas that of cephaloridine was 1.4 h. The degree of serum protein-binding was strikingly higher for cefazolin (81%) than for cephaloridine (24%), suggesting that the antibacterial activity of the former in serum might be less than that of cephaloridine after equal doses. This proved to be the case when the bacterial activity of blood drawn 1, 4, and 8 h after injection of the two drugs was examined.