bluuebunny/crossref_metadata_2025 huggingface dataset:
Agar medium for use in susceptibility testing of bacteria from human periodontal pockets
Authors: Walker C B , Niebloom T A , Socransky S S
Published: June 2012

An agar medium (medium V) was formulated to determine the minimal inhibitory concentrations (MICs) of antimicrobial agents for bacteria encountered in human periodontal pockets. The medium contained (per liter) Trypticase, 15 g; yeast extract, 5 g; sodium chloride, 5 g; glucose, 2 g; sodium pyruvate, 2 g; sodium formate, 1 g; sodium fumarate, 1.5 g; sodium succinate, 0.1 g; Tween 80, 0.25 ml; agar, 15 g; hemin, 5 mg; and menadione, 0.5 mg. The growth of 50 oral strains was compared on this and six other media which included: Wilkins-Chalgren agar, Schaedler agar, Brucella agar, Trypticase-soy blood agar, and Schaedler and Brucella agars supplemented with whole blood. Growth, for most strains, was greatest on medium V. Medium V was also compared with Wilkins-Chalgren agar, using the same oral strains, to determine the MICs of the following antibiotics: penicillin, tetracycline, chloramphenicol, clindamycin, and erythromycin. The MICs of these antibiotics were essentially the same on both media when growth was quantitatively similar.
Urinary casts as an indicator of renal tubular damage in patients receiving aminoglycosides
Authors: Schentag J J , Gengo F M , Plaut M E , Danner D , Mangione A , Jusko W J
Published: June 2012

We assessed the value of quantitative cast excretion as an early marker of renal tubular damage in 154 seriously ill patients. One hundred twenty-four of these received aminoglycoside antibiotics, and 30 of the 124 experienced a rise in serum creatinine of 0.5 mg/dl or more during therapy. The remaining 30 of the 154 patients were treated with other antibiotics and served as controls. Casts were quantitated in random urines collected before morning diuretic doses. Cast counts in control patients averaged 44 +/- 51 casts during the intensive care unit admission. Patients given aminoglycosides without a significant rise in serum creatinine of 0.5 mg/dl or more excreted 153 +/- 196 casts, significantly more than controls. In comparison to both the control and nontoxic patients, the 30 nephrotoxic patients excreted significantly more casts (625 +/- 364) and were significantly higher as early as 9 days before serum creatinine first rose. Daily urinary cast counts are a rapid and inexpensive means of identifying early renal tubular damage in critically ill patients given aminoglycosides.
Pharmacokinetics of cefamandole and ampicillin in experimental meningitis
Authors: Beaty H N , Walters E
Published: June 2012

The penetration of cefamandole and ampicillin into the cerebrospinal fluid of rabbits with and without pneumococcal meningitis was evaluated. In normal animals, a mean maximum concentration of 0.22 +/- 0.13 microgram of cefamandole per ml was measured in the spinal fluid after a dose of 150 mg/kg given intramuscularly; with 25 and 50 mg/kg doses, no antibiotic was detected in the cerebrospinal fluid. With ampicillin, in intramuscular doses of 200 and 300 mg/kg, the mean maximum concentrations encountered in the cerebrospinal fluid were 1.59 +/- 0.4 and 1.47 +/- 0.44 microgram/ml, respectively. Penetration of cefamandole, and to a lesser extent ampicillin, was increased after 24 h of experimental meningitis. With cefamandole, the concentration of drug in the cerebrospinal fluid exceeded the usual inhibitory concentration for Haemophilus influenzae only with the 150 mg/kg dose. After 48 h of meningitis, there was a trend toward higher levels of antibiotic in the cerebrospinal fluid, but the difference between animals infected 24 versus 48 h was not statistically significant. In animals with meningitis, serum concentrations after 150 mg of cefamandole per kg and both ampicillin doses studied were 32 to 38% lower than the serum levels achieved in normal rabbits after identical doses of antibiotic.
Effect of free fatty acids on liposome susceptibility to imidazole antifungals
Authors: Sud I J , Chou D L , Feingold D S
Published: June 2012

The presence of free fatty acids in liposome model membranes sensitizes these membranes to the action of the imidazole antifungals, clotrimazole, micronazole, and sulconazole. Unsaturation of the fatty acids is an important variable; the effect of linoleic and oleic acids is much greater than that of stearic acid. The imidazoles differ somewhat in action, with clotrimazole potency greatest both on membranes with and without fatty acids. Sulconazole has very little activity on membranes without fatty acids even at the highest concentrations tested. The data are discussed with reference to the susceptibility of various cells to the imidazoles and the specificity of imidazole action. A modification of the enzymatic method generally used for assay of marker glucose with liposome systems is also presented.
Hydrolysis of cefamandole nafate in dialysis patients
Authors: Nielsen R L , Wolen R , Luft F C , Ozawa T
Published: June 2012

The hydrolysis of cefamandole nafate was examined in vivo in five dialysis patients and five subjects with normal renal function. The plasma half-life of cefamandole was prolonged in the patients with renal failure compared with normal subjects (18.3 +/- 4.5 [standard deviation] versus 10.35 +/- 1.4 min, P less than 0.01). The pharmacokinetics of cefamandole nafate best fit two-compartment, open-model kinetics. We conclude that patients with severe renal failure are capable of hydrolyzing cefamandole nafate to cefamandole and formate at a rate sufficiently rapid so as not to allow an accumulation of cefamandole nafate. The difference in half-life may be related to urinary excretion of cefamandole nafate in normal individuals.
Bronchial Secretion Levels of Amikacin
Authors: Dull William L. , Alexander Michael R. , Kasik John E.
Published: June 2012

Amikacin was given to 14 noninfected men as three consecutive intramuscular injections (7.5 mg/kg) at 12-h intervals. Serum and bronchial secretion specimens were obtained at various times during flexible fiberoptic bronchoscopy after the final dose. Serum and bronchial secretion concentrations obtained between 1.5 and 2.0 h after the final dose ranged from 17 to 40 μg/ml and 2.3 to 8.4 μg/ml with a mean of 23.7 ± 2.9 and 5.23 ± 1.5 μg/ml, ±1 standard error of the mean, respectively. The highest bronchial secretion concentration in each subject correlated with the highest serum concentration (
r
= 0.83,
P
< 0.001), and all concurrent serum and bronchial secretion concentrations demonstrated a significant correlation (
r
= 0.82,
P
< 0.001). Clearance occurred at the same rate (half-life serum = 2.84 h; half-life of bronchial secretion = 2.60 h,
P
> 0.5). The mean bronchial secretion concentration of the 15 specimens obtained more than 7 h after the final dose was less than 1.0 μg/ml, with a range from 0.3 to 1.6 μg/ml. It is concluded that amikacin may achieve minimal inhibitory concentrations for many gram-negative bacteria in the bronchial secretions of noninfected patients 1 to 2 h after the final dose. However, levels fall below the reported minimal inhibitory concentrations against negative bacteria 6 to 7 h after the final dose. Furthermore, bronchial secretion levels may never reach the minimal inhibitory concentration against
Pseudomonas aeruginosa
.
Effects of Interferon and Adenine Arabinoside Treatment of Hepatitis B Virus Infection on Cellular Immune Responses
Authors: Hafkin Barry , Pollard Richard B. , Tiku Moti L. , Robinson William S. , Merigan Thomas C.
Published: June 2012

Fifteen patients with chronic hepatitis B were treated with adenine arabinoside (Ara-A) or human leukocyte interferon (HLI). Cellular immune response to hepatitis B virus surface antigen and antigens prepared from herpes simplex virus, varicella zoster virus, and cytomegalovirus was measured by a lymphocyte blast transformation assay and an assay for interferon production. Measurements were made before, during, and after antiviral treatment. Unlike patients convalescing from acute hepatitis B, only 2 of 15 patients with chronic hepatitis B had significant blast transformation to hepatitis B surface antigen. One such response occurred during the pretreatment period of HLI therapy, and the other was in a patient undergoing low-dose (<10
5
U/kg per day) HLI therapy. Mononuclear cell cultures were tested for interferon production in the presence of hepatitis B surface antigen. Cells from only 1 of 15 patients produced detectable levels of interferon. In contrast, all of these patients had normal cellular immune responses to herpesvirus antigens. Transformation responses to herpes antigens decreased three- to fivefold after patients were treated with >10
5
U of HLI per kg per day. Antiviral therapy with <10
5
U of HLI per kg per day or Ara-A did not produce a detectable depression of transformation response. Ara-A produced marked lymphocytopenia and a marked lymphocyte fragility after 5 or more days of therapy. In vitro Ara-A was toxic to lymphocytes at concentrations as low as 0.5 μg/ml. These changes in lymphocyte parameters may affect the outcome of antiviral therapy.
Susceptibility of Pseudomonas maltophilia to antimicrobial agents, singly and in combination
Authors: Felegie T P , Yu V L , Rumans L W , Yee R B
Published: June 2012

Pseudomonas maltophilia is resistant to most of the commonly used antimicrobial agents including those active against Pseudomonas aeruginosa. The susceptibility of 14 clinical isolates of P. Maltophilia to 18 antimicrobial agents was determined by broth dilution testing. All organisms were susceptible to trimethoprim-sulfamethoxazole (TMP-SMZ), minocycline, and LY127935. A total of 87 and 79% of the organisms were susceptible in vitro to colistin and chloramphenicol, respectively. With the exception of sisomicin, the organisms were resistant to the aminoglycosides. Of 21 combinations of antimicrobials examined for synergy, only the combination of TMP-SMZ with carbenicillin was consistently (86%) synergistic in vitro. Supplementation of the testing media with calcium and magnesium increased the minimal inhibitory concentrations for the aminoglycosides, the penicillins, and TMP-SMZ against P. maltophilia.
Temperature-sensitive 6-aminopenicillanic acid-resistant mutants of Escherichia coli
Authors: Ishiguro E E , Iwaya M , Turley W
Published: June 2012

Wild-type Escherichia coli cells became spherical in the presence of low concentrations of 6-aminopenicillanic acid (APA). Higher concentrations of APA caused inhibition of cell division (filamentation) and lysis. Spontaneous temperature-sensitive APA-resistant mutants were isolated and characterized. These mutants also possessed increased resistance to mecillinam but not to benzylpenicillin, ampicillin, and cephaloridine. They formed round or pleomorphic cells at the nonpermissive temperature and possessed thermolabile penicillin-binding protein 2 activity. Temperature-resistant revertants of these mutants had normal rod-shaped morphology, normal levels of sensitivity to APA and mecillinam, and thermostable penicillin-binding protein 2 activity. The mutation conferring APA resistance cotransduced with lip and mapped, therefore, close to 14 min on the E. coli linkage map. APA appears to be more specific than mecillinam as a selective agent for the isolation of penicillin-binding protein 2 mutants.
In vitro activity of LY127935, a new 1-oxa cephalosporin, against aerobic gram-negative bacilli
Authors: Delgado D G , Brau C J , Cobbs C G , Dismukes W E
Published: June 2012

A total of 434 clinical aerobic gram-negative bacillary isolates were tested against LY127935, a new 1-oxa cephalosporin, and compared with other cephalosporins, penicillins, and aminoglycosides by a broth microdilution technique. Cefotaxime (HR756), a new semisynthetic cephalosporin, and LY127935 were more active, and showed lower minimum inhibitory concentrations (ranges, less than or equal to 0.12 to 2.0 micrograms/ml), than cefamandole, cefoxitin, and cefazolin against Escherichia coli, Klebsiella spp., Enterobacter spp., Proteus mirabilis, indole-positive Proteus spp., Serratia marcescens, Providencia spp., and Citrobacter spp. Against P. aeruginosa, pepercillin, azlocillin, and mezlocillin were the most active beta-lactam agents; 64 micrograms/ml inhibited 99, 93, and 87% of the isolates, respectively. LY127935 and cefotaxime at 16 micrograms/ml inhibited 71% of Pseudomonas isolates, whereas the aminoglycosides gentamicin, tobramycin, and amikacin at a concentration of 4 micrograms/ml inhibited 84, 88, and 93%, respectively. Minimum bactericidal concentrations were determined for all isolates and were generally the same as the minimum inhibitory concentrations.
Effect of penicillin and virginiamycin on drug resistance in lactose-fermenting enteric flora
Authors: Gaines S A , Rollins L D , Williams R D , Selwyn M
Published: June 2012

Three groups of beagle dogs were fed either a control diet, a diet containing virginiamycin (55 microgram/g of diet), or a diet containing penicillin (110 microgram/g of diet). The proportions of lactose-fermenting organisms in their feces that were resistant to ampicillin, dihydrostreptomycin, tetracycline, or chloramphenicol were measured by a comparative plate-counting procedure. Both antibiotic-supplemented diets resulted in an increase (P < 0.001) in the occurrence of ampicillin, dihydrostreptomycin, and tetracycline resistances during the time of their administration. The occurrence of these resistances was greater (P < 0.001) in the group receiving penicillin than in the group receiving virginiamycin. In addition to the above resistances, a greater (P < 0.001) occurrence of resistance to a sulfonamide (sulfamethoxypyridazine) due to treatment was found by susceptibility testing of isolates. Representative isolates were able to transfer their resistance to a strain of Escherichia coli K-12.
Potentiation of the Antifungal Effects of Antibiotics by Amphotericin B
Authors: Kwan C. N. , Medoff G. , Kobayashi G. S. , Schlessinger D. , Raskas H. J.
Published: June 2012

Amphotericin B was found to potentiate the antifungal effects of mycophenolic acid glucuronide, tetracycline, and actinomycin D by increasing the penetration of these antibiotics through the fungal cytoplasmic membrane. Because the fungi were over 100 times more susceptible than animal cells to these effects of amphotericin B, these observations might have clinical application.
Butirosin, a New Aminoglycosidic Antibiotic Complex: Isolation and Characterization
Authors: Dion Henry W. , Woo Peter W. K. , Willmer Neil E. , Kern Donald L. , Onaga John , Fusari Salvatore A.
Published: June 2012

Butirosin, a new water-soluble aminoglycosidic antibiotic complex, active against gram-positive and gram-negative bacteria, has been isolated from fermentation filtrates of
Bacillus circulans
by ion exchange. The complex has been resolved into isomeric A and B components, C
21
H
41
N
5
O
12
, by means of Dowex 1 × 1 or Dowex 1 × 2 chromatography. Properties of the free bases and the
N, N′, N″, N‴
-tetraacetyl derivatives of butirosin A and B are given.
Phosphorylation of Lividomycin by
Escherichia coli
Carrying an R Factor
Authors: Yamaguchi Masahito , Koshi Tomoyuki , Kobayashi Fujio , Mitsuhashi Susumu
Published: June 2012

A lividomycin-phosphorylating enzyme from a lividomycin-resistant strain of
Escherichia coli
carrying an R factor was partially purified by fractionation with ammonium sulfate and Sephadex G-100 column chromatography. The enzyme inactivated, in the presence of adenosine triphosphate and Mg
2+
, several antibiotics having a
d
-ribose moiety linked to 2-deoxystreptamine, i.e., lividomycin A and B, neomycin, paromomycin, and vistamycin, but did not inactivate the kanamycins, streptomycin, or the gentamicin C components. Chemical studies of the inactivated product suggested that the phosphorylated site of the inactivated lividomycin was the hydroxyl group of the
d
-ribose moiety.
An Effect of Hydroxyurea on
Staphylococcus epidermidis
: Temporary Loss of Viability
Authors: Feiner Rose R. , Rosenkranz Herbert S. , Coward Joe E.
Published: June 2012

Although hydroxyurea (HU) is recognized as a specific inhibitor of deoxyribonucleic acid (DNA) synthesis, it did not have this effect in a strain of
Staphylococcus epidermidis
. In this case, HU caused a loss of colony-forming ability but did not prevent cell division in liquid medium. DNA synthesis apparently was affected only secondarily. About 10% of the population recovered colony-forming ability during the latter part of the growth cycle or when growth was slowed by chloramphenicol. Recovery also occurred when HU was removed from the medium. HU prevented cellular autolysis.
Comparison of Tobramycin, Gentamicin, Colistin, and Carbenicillin in
Pseudomonas
Sepsis in Monkeys
Authors: Saslaw Samuel , Carlisle Harold N. , Moheimani Mohammad
Published: June 2012

Intravenous inoculation of 3.4 × 10
10
to 7.4 × 10
10
Pseudomonas aeruginosa
organisms into rhesus monkeys 4 days after intravenous or intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate resulted in fatal sepsis in eight of nine monkeys. After intramuscular administration, in two equal doses, of 5 mg of tobramycin, gentamicin, and colistin per kg per day beginning 16 hr after challenge, 4 of 11, 4 of 11, and 3 of 10 monkeys died, respectively. Administration of daily doses of 100 to 400 mg of carbenicillin per kg was followed by death in 5 of 12. Duration of illness in the surviving monkeys in each therapy group was similar. Under the conditions of this study, prior administration of vincristine sulfate resulted in a decrease in leukocytes and enhanced susceptibility to
Pseudomonas
infection. Using this model for studies of comparative efficacy of antibiotics, we observed comparable results after treatment with tobramycin, gentamicin, colistin, and carbenicillin.
Correlation Between the Binding of β-Lactam Antibiotics to
Staphylococcus aureus
and Their Physical-Chemical Properties
Authors: Retsema James A. , Ray Verne A.
Published: June 2012

The rate of
14
C-benzylpenicillin (penicillin G) binding to
Staphylococcus aureus
Oxford cells increased with increasing hydrogen ion concentration. The extent of inhibition of
14
C-penicillin G binding caused by a competing
12
C-β-lactam antibiotic is a function of hydrogen ion concentration and can be correlated both with net charge of a competing
12
C-molecule and net charge of the
S. aureus
cell at a given
p
H. The ability of a β-lactam antibiotic to compete for
14
C-penicillin G-binding sites can generally be correlated with its hydrophobic nature. It is proposed that, although semisynthetic cephalosporins are chemically less reactive than penicillins, they are superior to benzylpenicillin in their ability to permeate the outer surface of the
Staphylococcus
cell wall and irreversibly bind to reactive sites.
Serum Protein Binding of the Aminoglycoside Antibiotics
Authors: Gordon Ralph C. , Regamey Claude , Kirby William M. M.
Published: June 2012

The binding of four aminoglycoside antibiotics by human serum was investigated under controlled conditions of physiological
p
H and temperature, by means of an ultrafiltration technique. No serum binding was demonstrable for gentamicin, tobramycin, or kanamycin, whereas streptomycin was 35% bound. Previous conflicting studies are discussed, and some of the pharmacological implications are considered.
Relative Incidence of Phlebitis Caused by Continuous Intravenous Infusion of Cephapirin and Cephalothin
Authors: Lane A. Z. , Taggart J. G. , Iles R. L.
Published: June 2012

In a single-blinded study, two groups of 10 healthy subjects were given cephapirin or cephalothin by continuous intravenous infusion for 5 days, 0.5 g every 6 hr for the first day and then 1.0 g every 6 hr for 4 days. Eight of the cephalothin subjects and two of the cephapirin subjects developed phlebitis. Phlebitis was more severe in the cephalothin group and developed more rapidly, necessitating vein changes six times more often than in the cephapirin group. The less irritating properties of cephapirin demonstrated in this study indicate it may be the more useful cephalosporin analogue for intravenous therapy.
Concentrations of Ampicillin and Chloramphenicol in the Serum of Patients with Acute
Salmonella
Enteric Fever
Authors: Mikhail Isis A. , Kent D. C. , Sorensen K. , Sanborn W. R. , Smith J.
Published: June 2012

Concentrations of ampicillin and chloramphenicol were measured in the serum of patients being treated for acute infections by
Salmonella typhi
or
S. paratyphi
A. Ampicillin was administered by the oral or intramuscular routes, whereas chloramphenicol was given orally only. Ampicillin concentrations were highest 1 hr after initiation of intramuscular therapy and 2 hr after oral administration. The serum concentration of ampicillin was significantly higher when it was given intramuscularly than when it was given orally. However, serum concentrations in orally treated patients were approximately the same at 1 hr after the fifth dose as they were 1 hr after the first dose, in contrast to intramuscularly treated patients, in whom the serum concentration of ampicillin was significantly lower 1 hr after the fifth dose. On the other hand, serum concentrations of chloramphenicol were significantly higher after the fifth dose than after the first dose. The rates of cure, relapse, and drug treatment failure were similar for all treatment regimens, and the drug concentrations attained in serum were generally above the minimal inhibitory concentration for the infecting salmonellae.
In Vitro Susceptibility of Isolates of
Aspergillus fumigatus
and
Sporothrix schenckii
to Amphotericin B
Authors: Brandsberg John W. , French M. Elaine
Published: June 2012

The in vitro susceptibility of 21 isolates of
Aspergillus fumigatus
and 12 isolates of
Sporothrix schenckii
to amphotericin B was determined. The minimal inhibitory concentration (MIC) for the
A. fumigatus
isolates ranged from 0.14 to 0.6 μg of drug per ml. The mean MIC for the 21 isolates was 0.33 μg per ml. The MIC for the 12
S. schenckii
isolates ranged from 0.68 to 2.12 μg of drug per ml, with a mean MIC of 1.38 μg per ml.
Aztreonam, cefoperazone, and gentamicin in the treatment of experimental Enterobacter aerogenes endocarditis in rabbits
Authors: Kobasa W D , Kaye D
Published: June 2012

The effectiveness of aztreonam, cefoperazone, and gentamicin alone and in combination was evaluated in Enterobacter aerogenes endocarditis in rabbits. The minimal inhibitory concentration/minimal bactericidal concentration ratios for E. aerogenes were as follows: aztreonam, 0.4/0.4 microgram/ml; cefoperazone, 0.8/0.8 microgram/ml; and gentamicin, 3.1/3.1 micrograms/ml. With an inoculum of 10(9) organisms per ml, aztreonam and cefoperazone were equivalent in reducing titers of E. aerogenes in broth, and both drugs demonstrated an increased rate of reduction when gentamicin was added; gentamicin alone was least effective. E. aerogenes endocarditis in rabbits was treated intramuscularly with aztreonam (60 mg/kg) every 6 h, with cefoperazone (60 mg/kg) every 6 h, with gentamicin (1.7 mg/kg) every 8 h, and with aztreonam plus gentamicin or cefoperazone plus gentamicin for 5 and 10 days, respectively. All of the therapeutic regimens were effective in reducing vegetation titers as compared with untreated controls. Aztreonam plus gentamicin was more effective than either aztreonam or gentamicin alone. Cefoperazone plus gentamicin was more effective than cefoperazone alone but was not more effective than gentamicin alone. Neither aztreonam and cefoperazone nor aztreonam and gentamicin differed significantly, but gentamicin was significantly more effective than cefoperazone. Aztreonam plus gentamicin did not differ significantly in effectiveness from cefoperazone plus gentamicin. Aztreonam gave a peak level of about 135 micrograms/ml and a half-life of 0.7 h. Cefoperazone gave a peak level of about 155 micrograms/ml and a half-life of 1.1 h. Gentamicin gave a peak level of 7.4 micrograms/ml and a half-life of 1.3 h.
Passicol, an Antibacterial and Antifungal Agent Produced by
Passiflora
Plant Species: Qualitative and Quantitative Range of Activity
Authors: Nicolls Joan M. , Birner J. , Forsell P.
Published: June 2012

Fungal molds and yeasts, an actinomycete, and gram-positive and gram-negative bacteria were tested qualitatively with an antimicrobial substance, here called “Passicol,” obtained from
Passiflora
species. A wide range of organisms were susceptible to Passicol. Some bacteria and a yeast were tested quantitatively by a broth dilution method. Passicol was nontoxic to mice and rabbits.
Tobramycin and Gentamicin Concentrations in the Serum of Normal and Anephric Patients
Authors: Lockwood W. R. , Bower John D.
Published: June 2012

The serum half-life of tobramycin was found to be the same as that of gentamicin in patients with similar renal function. The values ranged from 2 hr in normal volunteers to 53.4 hr in anephric patients. Both drugs were readily removed from the serum by the Kiil artificial kidney, with a 70% reduction in serum concentrations during a 12-hr dialysis period.
A9145, a New Adenine-Containing Antifungal Antibiotic: Fermentation
Authors: Boeck L. D. , Clem G. M. , Wilson M. M. , Westhead J. E.
Published: June 2012

A9145 is a basic, water-soluble, antifungal antibiotic which is produced in a complex organic medium by
Streptomyces griseolus
. The metabolite has a molecular weight of 510, and contains adenine as well as sugar hydroxyl and amino groups. Although glucose, fructose, glucose polymers, and some long-chain fatty acid methyl esters supported biosynthesis, oils were superior, with cottonseed oil being preferred. Several ions and salts, especially Co
2+
, PO
4
3−
, and CaCO
3
, were stimulatory. Adenine, nucleosides, and some amino acids increased the accumulation of A9145 in shaken-flask fermentors. Enrichment of the culture medium with tyrosine afforded maximal enhancement of antibiotic production in both flask and tank fermentors. Control of the dissolved O
2
level was also critical, the optimal concentration being 3 × 10
−2
to 4.5 × 10
−2
μmole of O
2
/ml. Optimization of various fermentation parameters increased antibiotic titers approximately 135-fold in shaken flask fermentors and 225-fold in stirred vessels.
Characterization of R Factor β-Lactamases by the Acidimetric Method
Authors: Rubin Fran A. , Smith David H.
Published: June 2012

The properties and regulation of β-lactamases produced by certain R factors derived from ampicillin-resistant strains of
Escherichia coli
and
Klebsiella
were characterized. β-Lactamase activity was determined by the acidimetric method with phenol red as indicator. The sensitivity of this assay was increased by employing phosphate buffer at a final concentration of 0.4 m
m
; as little as 0.05 unit (1 unit equals the amount of β-lactamase that hydrolyzes 1 μmole of benzyl penicillin per hr at
p
H 7.6 and 25 C) could be detected. This assay is rapid and convenient and appears to be superior to other methods currently employed to assay R factor β-lactamases. Two classes of β-lactamases were distinguished on the basis of substrate profile, heat inactivation, and
K
m
values. The regulation of most of these R factor β-lactamases, like certain other R factor enzymes, is subject to cyclic adenosine monophosphate-mediated catabolite repression.
Treatment of Herpes Simplex Virus Types 1 and 2 Encephalitis in Mice with 9-β-
d
-Arabinofuranosyladenine
Authors: Sloan B. J. , Miller F. A. , McLean I. W.
Published: June 2012

The susceptibility of herpes simplex type 1 and type 2 viruses to 9-β-
d
-arabinofuranosyladenine (ara-A) was tested in intracerebrally infected mice. Subcutaneously administered ara-A resulted in markedly equivalent and reproducible chemotherapeutic activity against both serotypes of herpes simplex viruses. Administration of ara-A by several different intermittent dosage regimens showed that change in pattern of response in terms of survivors appears to be influenced more by total amount of drug administered than by schedule or duration of drug treatment. In general, surviving drug-treated, virus-infected animals survived rechallenge with 1,000 LD
50
of the respective homologous virus inoculated intracerebrally on the 21st day after the initial virus inoculation. A neutralization test performed in vitro-in vivo confirmed the identity of the two distinct serotypes of herpes simplex virus employed. The data indicate that the genital form of herpes simplex virus (type 2) is as sensitive as the oral-mouth form (type 1) to the significant therapeutic activity of ara-A.
A Phenanthrene Methanol (WR 33063) for Treatment of Acute Malaria
Authors: Arnold J. D. , Martin D. C. , Carson P. E. , Rieckmann K. H. , Willerson D. , Clyde D. F. , Miller R. M.
Published: June 2012

WR 33063, a phenanthrene methanol, was studied in human volunteers for tolerance and toxicity. In normal volunteers, it was possible to give 4.6 g in four divided doses without adverse effect for 10 days. At this dose level, there was neither evidence of photosensitivity nor adverse renal or cardiac effect. At a dose level of 1.6 g in four divided doses for 6 days, WR 33063 cured 18 of 23 nonimmune volunteers infected with the Smith strain of
Plasmodium falciparum
from Vietnam. In addition, infections due to the Marks and Braithwaite Vietnam strains were also treated because these strains represent a major therapeutic challenge to chloroquine; six of six and two of three volunteers, respectively, were cured. With the Malayan Camp strain, 1.6 g in four divided doses for 6 days cured all of five volunteers. The African Uganda I strain of chloroquine-responsive malaria was even more responsive to WR 33063; all of six men who received 1.6 g in four divided doses for 6 days were cured, and all of three men who received this same dosage for 3 days were cured. One subject infected with a Haitian strain of
P. falciparum
was treated and cured. Blood-induced infections with the Chesson strain of
P. vivax
also responded well to WR 33063 with four of five men cured. In all, 52 men received WR 33063 in tolerance trials, and 59 men with experimental malaria and one man with clinical malaria were treated with WR 33063.
In Vitro Effect of 1-β-
d
-Ribofuranosyl-1,2,4-Triazole-3-Carboxamide (Virazole, ICN 1229) on Deoxyribonucleic Acid and Ribonucleic Acid Viruses
Authors: Huffman John H. , Sidwell Robert W. , Khare Gyaneshwar P. , Witkowski Joseph T. , Allen Lois B. , Robins Roland K.
Published: June 2012

Virazole (1-β-
d
-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a highly soluble new synthetic nucleoside having significant, reproducible activity against a broad spectrum of deoxyribonucleic acid and ribonucleic acid viruses in vitro. The drug inhibited viral cytopathogenic effects in monolayers of cells infected for 3 days with type 3 adeno, types 1 and 2 herpes, myxoma, cytomegalo, vaccinia, infectious bovine rhinotracheitis, types 1A, 2, 8, 13, and 56 rhino, types 1 and 3 parainfluenza, vesicular stomatitis, subacute sclerosing panencephalitis, Semliki Forest, Newcastle disease, and measles viruses. Hemagglutinin production by influenza A
2
, influenza B, and type 1 parainfluenza viruses in chicken embryo cells was reduced by Virazole treatment. Recoverable intra- and extracellular virus titers were reduced by the drug in experiments with type 1 herpes, vaccinia, type 3 parainfluenza, and vesicular stomatitis viruses. Plaque formation by type 1 herpesvirus was also inhibited by exposure of the infected cells to Virazole. Pretreatment of cells with the compound, followed by its removal before addition of type 1 herpesvirus, severely lessened the antiviral activity; the compound was still moderately effective in reducing the viral effects on the cells when added as long as 22 hr after the virus. Parallel experiments, in which the antiviral activity of a number of known active drugs was compared, indicated Virazole to have at least a comparable degree of activity, and it was also active against a wider variety of viruses than any of these known active materials. The CCED
50
of Virazole to chicken embryo cells was approximately 1,000 μg/ml, although concentrations as low as 10 μg/ml caused slight (15%) inhibition in total cellular protein after 72 hr of incubation.
Mutation of R Factors Capable of Specifying Hypersynthesis of Penicillinase
Authors: Odakura Yoshihiro , Tanaka Tokumitsu , Hashimoto Hajime , Mitsuhashi Susumu
Published: June 2012

When strains harboring R factor and showing ampicillin (APC) resistance were inoculated on plates containing various concentrations of APC, mutants carrying various levels of APC resistance occurred at high frequencies. Increases in the level of APC resistance were due to a quantitative increase in the formation of penicillinase. By conjugation experiments and transduction analysis, the mutation was found to affect the gene (
amp
) governing APC resistance on the R factor. The R-factor mutants carrying high and stable APC resistance were conjugally transferred at the same frequency as their parent R factors, and the level of their resistance to drugs other than APC was not distinct from that conferred by their parents. Such R-factor mutants could easily be obtained from wild-type R factors carrying low APC resistance. The hypersynthesis of penicillinase by such R-factor mutants was considered to be due to the replication of the
amp
gene on the R factor at hyper-rates and the integration of multiple copies of the
amp
gene (
amp
-hyper) in the R-factor genome.
Fungistatic Action of Juglans
Authors: Ahmad Shahnaz , Wahid Mukhtar A. , Bukhari A. Q. S.
Published: June 2012

A crude extract of the bark of
Juglans regia
Linn, tested against 13 species of fungi, showed selective fungistatic action against some species of the dermatophytes tested.
Antiviral Activity of Tobacco Smoke Condensate on Encephalomyocarditis Infection in Mice
Authors: Furusawa E. , Ramanathan S. , Suzuki N. , Tani S. , Furusawa S.
Published: June 2012

A water-soluble nontumorigenic acidic fraction of tobacco smoke condensate of cigarettes has been found to have antiviral activity against encephalomyocarditis (EMC) virus infection in mice. The portion of lower molecular weight was inhibitory to the growth of EMC virus, vesicular stomatitis virus, reovirus type 2, vaccinia virus, and poliovirus type 2, but not against adenovirus type 12, in KB cell cultures. The cigarette smoke agent did not induce serum interferon although it protected mice from EMC disease by pretreatment.
In Vitro Evaluation of a New Aminoglycoside Derivative of Kanamycin, BB-KA: a Comparison with Tobramycin and Gentamycin
Authors: Ries Kristen , Levison Matthew E. , Kaye Donald
Published: June 2012

Against more than 90% of 200 bacterial strains tested in vitro, the inhibitory concentration of gentamicin and tobramycin was 3.1 μg/ml and that of BB-K 8, a new semisynthetic aminoglycoside derivative of kanamycin, was 6.3 μg/ml.
Chloroquine-Resistant
Plasmodium falciparum:
Difference in the Handling of
14
C-Amodiaquin and
14
C-Chloroquine
Authors: Fitch Coy D.
Published: June 2012

14
C-amodiaquin and
14
C-chloroquine were used to study drug binding by preparations of owl monkey erythrocytes infected either with a chloroquine-susceptible (CS) or with a chloroquine-resistant (CR) strain of
P. falciparum
. Both of these drugs are derivatives of 4-aminoquinoline, but they differ in their side chains, and there are differences in the way they are handled by preparations of erythrocytes infected with malaria parasites. Although the apparent association constant for the binding of either drug is approximately 10
7
mol
−1
, two to three times more radioactivity was bound from
14
C-amodiaquin than from
14
C-chloroquine. Furthermore, there was no apparent difference between CS and CR parasites with respect to
14
C-amodiaquin binding, whereas erythrocytes infected with CR parasites have a deficiency of
14
C-chloroquine binding. This difference in the handling of amodiaquin probably accounts for its superiority in the treatment of the owl monkey and of humans infected with CR
P. falciparum
.
Enhanced Toxicity for Mice of Combinations of Bacterial Endotoxin with Antitumor Drugs
Authors: Marecki Nelda M. , Bradley S. G.
Published: June 2012

The toxicity of
Salmonella typhosa
0901W endotoxin to mice was potentiated by (per kilogram) 1 mg of colchicine, 20 mg of emetine, 100 mg of 6-mercaptopurine, 100 mg of 6-methylmercaptopurine riboside, 75 mg of methotrexate, 2 mg of sparsomycin, or 2.5 mg of vinblastine. No potentiation of endotoxin lethality was evident with simultaneously administered (per kilogram): 200 mg of cytosine arabinoside, 450 mg of dibromomannitol, 100 mg of 5-fluorouracil, 125 mg of 5-fluorouracil deoxyriboside, 8 mg of mitomycin C, 1 mg of nitrogen mustard, or 10 mg of tris(1-aziridinyl)-phosphine sulfide. With the exception of colchicine, all drugs prolonged the duration of sleep after the administration of 80 mg of hexobarbital per kg. Simultaneous injection of endotoxin with 100 mg of 6-mercaptopurine per kg, 75 mg of methotrexate per kg, or 1 mg of vincristine per kg resulted in significantly greater lethality than administration either prior to or after the drug. However when endotoxin was administered prior to 100 mg of 5-fluorouracil per kg, lethality was significantly increased. The route of administration of endotoxin and 5-fluorouracil, 6-mercaptopurine, methotrexate, or vincristine did not influence overall lethality. Pretreatment of mice with multiple doses of
Escherichia coli
endotoxin resulted in a significant reduction in the lethality of 6-mercaptopurine- or vincristine-endotoxin combinations, but had no influence on 5-fluorouracil- or methotrexate-endotoxin combinations. Endotoxin-pretreated mice were more susceptible to vincristine alone and more resistant to high doses of 5-fluorouracil. The lethality of 6-mercaptopurine was increased by simultaneous administration of gram-negative isolates from feces of human patients with neoplastic disease.
Characteristics of R931 and Other
Pseudomonas aeruginosa
R Factors
Authors: Bryan L. E. , Semaka Shirley D. , Elzen H. M. Van Den , Kinnear J. E. , Whitehouse R. L. S.
Published: June 2012

R factors were detected in 3.3% of 233 hospital isolates of
Pseudomonas aeruginosa
using
P. aeruginosa
recipients in conjugations. Transferred markers included streptomycin, tetracycline, and sulfonamide resistance. Gentamicin resistance was transferred from two strains previously shown to acetylate gentamicin. A group of R factors exemplified by R931 were characterized by failure to transfer to
Escherichia coli
recipients. Such R factors formed a single compatibility group when examined in a
P. aeruginosa
recipient. Other
P. aeruginosa
R factors, including RP4, showed stable coexistence with the R931 group. It is proposed that RP4 and similar R factors be members of the P-1 compatibility group and that R931, R3108, R209, and R130 be members of a group termed P-2. The buoyant densities of all R factors examined were similar, about 1.716 to 1.719 g/cm
3
. The content of R-factor deoxyribonucleic acid (DNA) relative to the total DNA varied among the different R factors, ranging from about 18 ± 2% in log-phase cells of 931 (R931) to undetectable for 679 (R679). However, R679, which transferred from strain 679 at extremely low and irregular frequencies to an
E. coli
host, was shown to represent about 4% R-factor DNA in that host. The relative DNA content of R931 appeared to decline in the stationary growth phase of 931 (R931) or 280 (R931). R931 covalently closed circular DNA was isolated by ethidium bromide-CsCl gradient centrifugation and examined by electron microscopy. Two major molecular distributions existed, having contour lengths of 0.5 and 12.4 μm. The molecular weights were estimated to be 10
6
and 25 × 10
6
. Both molecules were under relaxed replication control. R factor R931 exists as a naturally occurring high-frequency transfer system in
P. aeruginosa
strains 931 and 1310. However, in strain 280 it acts as if subject to fertility repression. Other members of the P-2 compatibility group also are high-frequency transfer systems in the natural host and in strain 1310. RP4 is restricted from recipient strain 1310. Some additional recipient effects were noted in that strains 1310 or 280 sometimes differed in recipient effectiveness with a given donor. Agglutination reactions with absorbed antiserum were able to distinguish between two members of the same R-factor compatibility group, R931 and R3108.
Antibacterial Activity of Cefamandole, a New Cephalosporin Antibiotic, Compared with that of Cephaloridine, Cephalothin, and Cephalexin
Authors: Eykyn Susannah , Jenkins Clare , King Anna , Phillips Ian
Published: June 2012

The in vitro antibacterial activity of cefamandole, a new cephalosporin antibiotic, was compared with that of cephaloridine, cephalothin, and cephalexin against 1,213 strains of gram-positive and gram-negative bacteria recently isolated from clinical sources. The decreasing order of activity of the four agents against gram-positive cocci was cephaloridine, cephalothin, cefamandole, and cephalexin. However, cefamandole was the most active of the four against
Haemophilus
species and gram-negative bacilli susceptible to cephalosporins. It was also active against many strains resistant to the other cephalosporins, such as
Enterobacter
species and indole-positive
Proteus
species, but there was a marked inoculum effect with all of these organisms, and minimal bactericidal concentrations were usually considerably higher than minimal inhibitory concentrations. Cefamandole, like other cephalosporins, had no useful activity against
Pseudomonas
species.
Toxicological, Pathological, and Teratological Studies in Animals with Cephradine
Authors: Hassert G. L. , DeBaecke P. J. , Kulesza J. S. , Traina V. M. , Sinha D. P. , Bernal E.
Published: June 2012

Cephradine, a semisynthetic cephalosporin antibiotic, has a low order of oral and parenteral toxicity in animals. The oral LD
50
in mice and rats ranged from 5 to >8 g/kg, and the intraperitoneal LD
50
values in mice and rats were 0.7 to 1.5 g/kg and 4.0 g/kg, respectively. The intravenous LD
50
in mice ranged from 3.0 to 3.8 g/kg. In anesthetized dogs, intravenous doses of cephradine (40 and 120 mg/kg, given 45 min apart) had no effect on either the renal or cardiovascular systems. Single intramuscular injections (0.25 ml or 0.5 ml of a solution containing 125 to 235 mg of cephradine/ml) elicited no signs of either pain or local irritation in dogs, and only transient signs of slight-to-moderate irritation were observed in rabbits. In subacute toxicity studies, cephradine was administered for 4 weeks to rats (daily intraperitoneal doses of 160, 480, or 1,600 mg/kg) and dogs (daily intravenous doses of 80, 240, or 800 mg/kg); in addition, over a 2-week period, monkeys were given daily intravenous doses of 60, 180, or 600 mg/kg. No clinical, biochemical, gross, or micropathological changes due to cephradine were observed in these animals; especially notable was the absence of any signs of nephrotoxicity. In chronic toxicity studies, daily doses of cephradine were administered orally to rats (100 to 1,000 mg/kg), dogs (50 to 500 mg/kg), and monkeys (50 to 500 mg/kg) for 26, 26, and 13 weeks, respectively. Significant responses were observed only in rats, in which grossly enlarged, but histologically normal, ceca developed, a common finding in rodents dosed with antibiotics; in addition, there were increases in the relative and absolute weights of the adrenal glands. None of these effects was observed in rats that were necropsied 3 weeks after termination of dosage. In reproduction studies in mice and rats given either daily oral doses (100 or 300 mg/kg) or daily intraperitoneal doses (rats only; 80 or 320 mg/kg) of cephradine, no drug-related teratogenic changes in the offspring were observed.
Enhanced Toxicity for Mice of Pactamycin with Bacterial Endotoxin
Authors: Bradley S. G. , Rose W. C.
Published: June 2012

Combinations of pactamycin and
Salmonella typhosa
0901 endotoxin, administered simultaneously, killed more BALB/c mice than comparable doses of either agent alone The slopes of the dose-response curves for combinations of endotoxin and pactamycin were parallel to both that for endotoxin alone and the antitumor drug alone; therefore, no new mechanism of toxicity has been evoked by the combination. The synergistic toxicity of endotoxin and pactamycin was due to an in vivo interaction rather than a direct reaction between the two agents. Phenobarbital pretreatment protected the mice from toxicity of the antitumor agent alone but not from the lethal action of the combination. Pretreatment with endotoxin increased the resistance of the mice to both endotoxin alone and the combination. Third agents unable to protect mice from the synergistic toxicity of endotoxin and pactamycin were α[
p
-(fluoren-9-ylidenemethyl)-phenyl]-2-piperidine-ethanol, neomycin, phenylbutazone, polymyxin B, and tybamate. Prednisolone pretreatment alleviated the toxicity of the combination. For the restricted series of killed bacteria and bacterial products tested for capability to enhance the toxicity of pactamycin, only gram-negative bacterial cells were potent. These results indicated that pactamycin rendered the mice more susceptible to endotoxin and that endotoxin was the causal lethal agent.
Influence of endotoxin on the intracortical accumulation kinetics of gentamicin in rats
Authors: Tardif D , Beauchamp D , Bergeron M G
Published: June 2012

The mechanism by which endotoxin (lipopolysaccharide [LPS]) modifies the intrarenal distribution and the nephrotoxic potential of gentamicin is unknown. We studied the influence of LPS on the intracortical accumulation kinetics of gentamicin in rats infused intravenously for 6 h, during which time steady-state levels of the antibiotic in serum were achieved. We compared gentamicin accumulation rates (V) in normal rats and in rats receiving LPS (0.5 and 5 mg/kg) as levels in serum (S) varied from 0.5 to 130 micrograms/ml. The pharmacokinetic parameters of gentamicin were previously measured in the three groups of rats that were studied in order to reach and maintain in each rat the desired levels of antibiotic in serum during the 6 h of infusion. Two hours before the infusion of gentamicin, LPS was injected intravenously over a period of 15 min. In normal rats, the increase in S was associated with a nonlinear increase in V. The Michaelis-Menten kinetics, which was the best-fitting function, gave an apparent Vmax (maximal capacity of uptake) of 195.03 +/- 9.75 micrograms/g per h and an apparent Km (concentration in serum at Vmax/2, an index of affinity) of 34.91 +/- 4.45 micrograms/ml (linear transformation of the experimental data by the Hanes-Woolf plot: r = 0.93, n = 85). In the rats that received LPS, the increase in S was associated with a linear increase of V: for LPS at 0.5 mg/kg, V = 27.00 + 1.50 S (r = 0.94, n = 80); for LPS at 5 mg/kg, V = 22.72 + 1.48 S (r = 0.94, n = 75). We conclude that endotoxin modifies the accumulation kinetics of gentamicin in the kidney cortices of rats.