bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Diuretics on Urinary Excretion of Cephalothin in Humans
Authors: Tice Alan D. , Barza Michael , Bergeron Michel G. , Brusch John L. , Weinstein Louis
Published: June 2012

Diuretics and antibiotics are frequently used concomitantly. The possibility of drug interactions led us to study the effects of several diuretics on the renal elimination of cephalothin. Five healthy volunteers received a constant infusion of 500 mg of sodium cephalothin per h for 9 h on 4 consecutive days. Each day, after the third hour of infusion, the subjects were given one of the following in varying order: (i) furosemide (1 mg/kg, intravenous), (ii) mercaptomerin (250 mg, intramuscular), (iii) mannitol (25 g, intravenous), or (iv) no diuretic (control day). Fluid losses were replaced hourly. Serum and complete urine collections were obtained each hour and assayed for creatinine and cephalothin (bioassay). Clearances (milliliter per minute) and urinary excretions (milligram per hour) of cephalothin did not differ either when the diuretic day values were compared with control day, or when pre- and postdiuretic results on the same day were compared. Creatinine clearances were not affected by diuretics except for a transient rise after furosemide.
Effects of Adenine Arabinoside on Cellular Immune Mechanisms in Humans
Authors: Steele Russell W. , Chapa Isidoro A. , Vincent Monroe M. , Hensen Sally A. , Keeney Ronald E.
Published: June 2012

In vitro lymphocyte blastogenic responses to the commonly employed mitogens, phytohemagglutinin, pokeweed, and concanavalin A, were evaluated when adenine arabinoside (ara-A) in a concentration of 3 μg/ml was added to the culture materials. Similarly, blastogenic and cytotoxic responses to cell cultures persistently infected with herpes simplex virus 1, herpes simplex virus 2, and varicella-zoster virus were determined in the presence of ara-A. No depression of these cellular immune responses by ara-A was demonstrated. This was in contrast to the effect of cytosine arabinoside, which at a concentration of 3 μg/ml severely inhibited these immune responses. Further studies examined lymphocyte blastogenic responses to the mitogens and blastogenic and cytotoxic responses specific for the herpes group virus infecting patients who were subsequently treated with ara-A; determinations were made before, during, and after treatment. In vitro responses during and after treatment with ara-A were unchanged or often enhanced as compared to pretreatment values. Therefore, the antiviral chemotherapeutic agent, ara-A, does not appear to depress the host's cellular immune responses, which are vital to successful elimination of invading herpes group viruses.
Improved Acetylating Radioenzymatic Assay of Amikacin, Tobramycin, and Sisomicin in Serum
Authors: Stevens Paul , Young Lowell S. , Hewitt William L.
Published: June 2012

The acetylating radioenzymatic assay of aminoglycosides was modified by using [
3
H]acetyl coenzyme A as cosubstrate. This modification reduces the cost of the method by at least one-half without sacrificing rapidity or accuracy.
Effect of pH and Human Serum on the Susceptibility of Group D Streptococci (Enterococci) to Ampicillin In Vitro
Authors: Gilbert D. N. , Eubanks N.
Published: June 2012

The in vitro susceptibility of group D streptococci (enterococci) to ampicillin was studied comparing the results obtained in Mueller-Hinton broth (MHB) with those obtained in normal human serum (NHS). The rate of enterococcal killing was consistently faster in NHS than in MHB at equivalent ampicillin concentrations. Whereas an increasing media pH appeared to decrease the susceptibility of enterococci to ampicillin by determinations of the minimum bactericidal concentration (MBC) of ampicillin, an opposite increase in susceptibility was observed when the rate of bactericidal activity was studied. This difference may be explainable by the instability of ampicillin at higher pH values. In both MHB and NHS a paradoxical decrease in the rate and extent of enterococcal killing occurred as the ampicillin concentration was increased above the minimally effective concentration. These results demonstrate the inadequacies of the MBC test system and the need for standardizing test media used for determining the susceptibility of enterococci to ampicillin.
Antibiotic Resistance Patterns of Clinical Isolates of
Serratia marcescens
Authors: Cooksey Robert C. , Bannister Edward R. , Farrar W. Edmund
Published: June 2012

Antimicrobial susceptibility patterns of 102 clinical isolates of
Serratia marcescens
from three medical centers were studied by using disk sensitivity and agar dilution methods. The least resistance was demonstrated against gentamicin, nalidixic acid, chloramphenicol, and sulfisoxazole, all of which inhibited more than 80% of the strains. Cephalothin was completely ineffective, and more than 90% of strains were resistant to ampicillin and tetracycline. As demonstrated by the agar dilution method, the minimal inhibitory concentration of nalidixic acid, gentamicin, tobramycin, and chloramphenicol for most strains fell within therapeutically attainable concentrations. The prevalence of resistance to ampicillin, cephalothin, and tetracycline was nearly the same at all three medical centers, whereas there appeared to be patterns characteristic for each center with regard to the other drugs used. Eleven of the isolates produced pigment and exhibited patterns similar but not identical to those of the nonpigmented strains, all 11 being resistant to between three and six drugs. Half of the strains were resistant to five or more antibiotics, indicating that some
Serratia
exhibit resistance to an unusually broad range of therapeutic agents.
Antibiotic Susceptibility Testing of Gram-Negative Nonfermentative Bacilli
Authors: Ruddell K. A. , Anselmo C. R.
Published: June 2012

A study was undertaken to determine if current methods of antibiotic susceptibility testing could be successfully applied to the gram-negative nonfermentative bacilli. Using clinical isolates and reference strains, experiments were conducted on the inherent reliability of the Bauer-Kirby method, as well as the effect of certain modifications on the method such as elimination of the 2- to 5-h incubation in broth and use of different agar media. Results obtained using these modifications were compared to the results obtained by the standard method. It was shown that the two modifications investigated had a significant effect on the interpretation of zone diameters. It was further shown that the standard Bauer-Kirby method with some exceptions correlates with minimal inhibitory concentrations as determined by broth dilution methods. Results suggest that the Bauer-Kirby method may be a reliable technique for testing the antibiotic susceptibility of the nonfermentative bacilli.
Nalidixic Acid and Macromolecular Metabolism in
Tetrahymena pyriformis
: Effects on Protein Synthesis
Authors: de Castro J. F. , Carvalho J. F. O. , Moussatché N. , de Castro F. T.
Published: June 2012

A study on the effect of nalidixic acid on macromolecular metabolism, particularly of protein, in
Tetrahymena pyriformis
was performed. It was shown that the compound is a potent inhibitor of deoxyribonucleic acid, ribonucleic acid, and protein synthesis for this organism. A conspicuous breakdown of polysomes, accompanied by the accumulation of 80
S
ribosomes, occurred in cells incubated for 10 min with the drug; polysome formation was prevented. The accumulating 80
S
particles were shown to be run-off ribosomal units. The incorporation of amino acids by a cell-free system is not affected by nalidixic acid. In nonproliferating cells the incorporation was also not prevented, unless the cells were previously incubated with the drug. These results are discussed in terms of the possible mechanism of action of nalidixic acid in
T. pyriformis
.
Epidemiology of Antibiotic and Heavy Metal Resistance in Bacteria: Resistance Patterns in Staphylococci Isolated from Populations Not Known to be Exposed to Heavy Metals
Authors: Groves David J. , Young Frank E.
Published: June 2012

Staphylococci were isolated from clinical specimens obtained from patients not known to be exposed to abnormal levels of heavy metals. The antibiotic and heavy metal resistance patterns of these strains were determined by using a disk diffusion test and computer sorting. Though not absolute, an association of resistance to mercury and tetracycline in coagulase-negative strains was found, in contrast to resistance to copper and penicillin in coagulase-producing strains. A high degree of correlation was observed between the resistance to phenyl mercury and inorganic mercury, but no correlation was obtained between resistance to methylmercury and other metals. In general, strains resistant to many agents were usually coagulase negative. A possible mechanism and implications of these associations are considered.
Glutamate Dehydrogenase Specific Activity and Cephalosporin C Synthesis in the M8650 Series of
Cephalosporium acremonium
Mutants
Authors: Queener S. W. , McDermott J. , Radue A. B.
Published: June 2012

Conditions for the accurate measure of glutamic dehydrogenase (GDH) from
Cephalosporium acremonium
were determined.

K
m

values for α-ketoglutarate and ammonium ion were 7 and 15 mM, respectively. The half-saturation for reduced nicotinamide adenine dinucleotide phosphate was 5 μM. Reduced nicotinamide adenine dinucleotide did not serve as a cofactor for the enzyme. The specific activity of GDH was measured in six mutants of
C. acremonium
which varied in their ability to synthesize cephalosporin C. The mutants represented two separately derived lines, A and B. The four mutants in line B were characterized by a derepression of the GDH upon entry into stationary phase. The two mutants in line A were characterized by repressed levels of GDH during the same period. Both lines exhibited high GDH activity early in their fermentations, but activity decreased during the period of active cell growth. Cytochrome
c
concentrations followed the same pattern as total soluble intracellular protein. Line A mutants were low in cephalosporin C productivity and line B encompassed low, intermediate, and high productivity mutants. The relative frequency of yield improvements in line A and B indicate that the altered regulation pattern for GDH in line B may have removed a nitrogen limitation for cephalosporin C synthesis.
Genetic Analysis of Drug Resistance in
Neisseria gonorrhoeae
: Identification and Linkage Relationships of Loci Controlling Drug Resistance
Authors: Maier Thomas W. , Zubrzycki Leonard , Coyle Marie B.
Published: June 2012

The genetic basis of multiple drug resistance of
Neisseria gonorrhoeae
was investigated by the technique of transformation. Six different genetic loci were characterized by the type and amount of antibiotic resistance they controlled, and also by the degree of linkage to other resistance markers. A streptomycin resistance locus is linked to separate loci determining resistance to tetracycline, chloramphenicol, and erythromycin. A multiple resistance locus was identified. This genetic locus determines resistance to a variety of antibacterial agents. Lastly, a locus determining resistance to the penicillins was found which is unlinked to any other resistance locus.
Assessment of Susceptibility of Ampicillin-Resistant Enterobacteria to Cephalosporins
Authors: Greenwood D. , Teoh Ching Haan , O'Grady F.
Published: June 2012

The susceptibility of 103 ampicillin-resistant strains of enterobacteria to two cephalosporins was assessed by turbidimetric monitoring and disk diffusion tests. The results obtained suggest that in most cases a correlation exists between the suppression of growth of a dense bacterial culture for a therapeutically acceptable period by a fixed, high concentration of cephalosporin and a large zone of inhibition (≥24 mm) using a high potency disk. This correlation was found to hold good when a moderate, subconfluent inoculum and commercially obtained blood-agar plates were used for the disk test, but not when the stringent conditions required by the Kirby-Bauer test (which demands a dense inoculum on Mueller-Hinton agar) were employed. Better correlation was obtained with cephaloridine than with cephalothin. This approach to the interpretation of disk diffusion tests gives a grossly different picture of the susceptibility of ampicillin-resistant enterobacteria to cephalosporins than do conventional minimal inhibitory concentration-based correlations.
Interrelation Between Guanosine Tetraphosphate Accumulation, Ribonucleic Acid Synthesis, and Streptomycin Lethality in
Escherichia coli
CP78
Authors: Sakai Ted T. , Cohen Seymour S.
Published: June 2012

The effects of streptomycin on the synthesis of ribonucleic acid (RNA) and guanosine-3′-diphosphate-5′-diphosphate have been examined in the isogenic strains CP78 (
rel
+
) and CP79 (
rel
−). In the absence of the required amino acids arginine, leucine, or threonine, streptomycin stimulates RNA synthesis in CP78 and this stimulation coincides with cell death. However, in the absence of histidine, also a required amino acid, streptomycin kills the cells without stimulation of RNA synthesis above that which occurs in the absence of streptomycin. In all of these instances, guanosine-3′-diphosphate-5′-diphosphate levels vary inversely with RNA synthesis, decreasing when a stimulation of RNA synthesis occurs. Streptomycin has little effect on guanosine-3′-diphosphate-5′-diphosphate levels in CP78 in the absence of histidine. Another histidine auxotroph, 15 T
−
H
−
U
−
(
rel
+
), does show streptomycin-stimulated synthesis of RNA which is coincident with cell death. CP79 (
rel
−
) is 10 times more susceptible to streptomycin than CP78 and streptomycin causes an inhibition of the relaxed synthesis of RNA. The greater susceptibility of CP79 may be due to a greater initial uptake of streptomycin by CP79.
Comparison of Sisomicin and Gentamicin in Bacteriuric Patients with Underlying Diseases of the Urinary Tract
Authors: Klastersky Jean , Hensgens Colette , Gerard Michel , Daneau Didier
Published: June 2012

Sisomicin and gentamicin (2 mg/kg) were administered in a random fashion to patients with bacteriuria superimposed on abnormalities of the urinary tract. Cure was achieved in a similar number of patients in both groups, but superinfection and reinfection with resistant microorganisms was more frequent in patients receiving gentamicin. Untoward side effects were not frequent in this series, especially if the serious underlying urological disease of most patients is taken into consideration. The susceptibility of the causative pathogens to the antibiotic administered and the severity of the underlying disease were the most important factors in the outcome.
Inhibition of
Coccidioides immitis
In Vitro and Enhancement of Anticoccidioidal Effects of Amphotericin B by Polymyxin B
Authors: Collins M. S. , Pappagianis D.
Published: June 2012

Growth of the spherule phase of
Coccidioides immitis
in liquid glucose-mineral salts medium was suppressed for 13 days by 5 to 10 μg of polymyxin B per ml. Inhibition of growth was also noted when filter paper disks containing polymyxin B were placed on the surface of arthrospore-seeded defined medium solidified with refined agar. The antibiotic evidently damaged the cytoplasmic membrane inasmuch as spherules suspended in distilled water containing 10 μg of polymyxin B per ml rapidly lost nucleotides. Leakage of nucleotides was prevented by 0.1 M Ca
2+
. The anticoccidioidal activity of amphotericin B (0.02 to 0.08 μg/ml) was enhanced by 2.5 μg of polymyxin B per ml. Colistin (polymyxin E) methanesulfonate did not inhibit spherule growth at concentrations as high as 50 μg/ml. This may be because colistin, though structurally similar to polymyxin B, is not cationic because its γ-amino groups are masked by methanesulfonate radicals.
Antibiotic G-418, a New Micromonospora-Produced Aminoglycoside with Activity Against Protozoa and Helminths: Antiparasitic Activity
Authors: Loebenberg David , Counelis Mae , Waitz J. Allan
Published: June 2012

Antibiotic G-418 was shown to be superior to paromomycin and metronidazole in cecal amoebiasis. Of particular interest was the high degree of activity seen with a relatively short treatment at low levels. Although the antibiotic was trichomonacidal in vitro at low levels, in vivo results indicated that at levels tested the antibiotic did not always affect cures. The antibiotic appears to have promise as an anticestode agent, being more active than paromomycin against
Hymenolepis nana
and active as a single oral dose at low levels against
Taenia
spp.
Accessibility of the [
14
C]Benzylpenicillin Binding Proteins in Membranes of Sporulating Bacilli
Authors: Hamilton Thomas E. , Lawrence Paul J.
Published: June 2012

Triton X-100 treatment or freeze-thawing damages the membranes of sporulating or vegetative cells as seen by protein leakage from cells. A 40% increase in the specific [
14
C]benzylpenicillin-binding capacity of detergent-treated or frozen sporulating cells was observed. Neither freezing nor Triton X-100 treatment of vegetative cells produced a detectable effect on their [
14
C]benzylpenicillin-binding capacity. These data indicate the presence of penicillin-binding sites in intact sporulating bacilli not accessible to penicillin in routine binding assays. The chemical specificity of [
14
C]benzylpenicillin binding to detergent-treated sporulating cells is similar to that observed with untreated vegetative or sporulating cells.
Diffusion of Trimethoprim and Sulfamethoxazole from Susceptibility Disks into Agar Medium
Authors: Grace M. E. , Bushby S. R. M. , Sigel C. W.
Published: June 2012

The standard practice of using a single susceptibility disk for the antimicrobial combination Septra (trimethoprim/sulfamethoxazole) has been further justified by a direct measurement of the diffusion rates of each compound through agar medium. [
14
C]trimethoprim and [
35
S]sulfamethoxazole, singly and in combination, were applied to blank susceptibility disks which were incubated on 4-inch (10.16-cm) agar plates (Mueller-Hinton medium) at 37 C. The migration of each compound from the disk and diffusion through agar were measured with time by determining the radioactivity in concentric zones extending from the origin. The two compounds diffuse with similar rates, maintaining approximately a 1:20 concentration ratio which is approximately the ratio of trimethoprim to sulfamethoxazole observed in plasma during treatment. The diffusion rate is independent of the presence of the other compound; greater than 95% of the radioactivity is transferred from the disk to the agar in 24 h.
Effects of Renal Failure and Dialysis on Cefazolin Pharmacokinetics
Authors: Madhavan T. , Yaremchuk Kathy , Levin Nathan , Fisher Evelyn , Cox Frank , Burch Keith , Haas Erwin , Pohlod Don , Quinn Edward L.
Published: June 2012

Serum and urinary levels of cefazolin were determined after a 500-mg parenteral dose in eight azotemic volunteers. The mean peak serum concentration was 1.5 to 5 times the levels obtained in nonazotemic patients. The serum half-life of cefazolin was increased significantly. In patients on dialysis, the mean serum half-life of cefazolin was 4.05 h during (or after) hemodialysis, and 32.1 h during (or after) peritoneal dialysis. There was a significant decrease in cefazolin removal when dialysate flow or membrane surface area of the dialyzer were decreased. It was also shown that one circuit through the dialysis unit caused measurable decrease in cefazolin concentration. These data and previously published reports suggest: (i) the maintenance dose of cefazolin can be decreased in azotemic patients; (ii) patients on hemodialysis will require an additional half dose after dialysis because of efficient removal during hemodialysis; and (iii) patients on peritoneal dialysis do not require an extra dose.
Bacteriocinogenic Clo DF13 Minicells of
Escherichia coli
Synthesize a Protein That Accounts for Immunity to Bacteriocin Clo DF13: Action of the Immunity Protein In Vivo and In Vitro
Authors: Kool A. J. , Borstlap A. J. , Nijkamp H. J. J.
Published: June 2012

The Clo DF13 plasmid-specific immunity protein is able to prevent the inhibitory effect of cloacin DF13 on in vitro protein synthesis. We have shown, by gel filtration, that direct binding of the Clo DF13 immunity protein to cloacin occurs in vitro. This cloacin DF13-immunity protein complex is rather stable, and the cloacin present in the complex is no longer able to cause inhibition of in vitro protein synthesis. The binding of immunity protein to cloacin DF13 is rather specific because the Clo DF13 immunity protein does not bind to in vitro inactive cloacin and binds very poorly to the closely related bacteriocin colicin E3. Furthermore, we present data which strongly suggest that in vitro at least a fourfold excess of immunity protein is required to ensure that every cloacin molecule is inactivated by cloacin-immunity protein complex formation. Only a fraction (an about equimolar amount) of the immunity protein molecules, however, actually binds to cloacin DF13. The existence of an immunity protein-cloacin complex in vivo was concluded from the observation that cloacin, purified by chromatography on diethyl-(2-hydroxypropyl)-aminoethyl Sephadex in the absence of urea, contains an about equimolar amount of a second protein which comigrates with immunity protein on sodium dodecyl sulfate-polyacrylamide and urea-polyacrylamide gels. In an in vitro protein-synthesizing system, this component appeared to behave identical to the Clo DF13 immunity protein. The purified immunity protein-containing cloacin was at least 80 times less active in inhibiting in vitro protein synthesis, compared to cloacin, free of immunity protein. These data imply that few, if any, cloacin DF13 molecules are present in cloacinogenic cells as active, free cloacin molecules.
Susceptibilities of Gram-Negative Bacteria to Combinations of Antimicrobial Agents In Vitro
Authors: Leng Bernard , Meyers Burt R. , Hirschman Shalom Z. , Keusch Gerald T.
Published: June 2012

Combinations of either clindamycin or erythromycin with gentamicin, colimycin, or carbenicillin were studied for their antimicrobial effects on clinical isolates of
Escherichia coli, Klebsiella
sp.,
Proteus mirabilis, Serratia marcescens, Enterobacter aerogenes
, and
Pseudomonas aeruginosa
. No antagonistic effects of the antibiotic combinations were observed. Synergistic effects of the antibiotic combinations were noted against most strains of
E. coli
tested, especially when either clindamycin or erythromycin was combined with gentamicin or colimycin. Of 16 other combinations of antibiotics examined with strains of
E. coli
as the test organisms, only the combination of penicillin G with either gentamicin or colimycin showed consistent synergy. The marked synergy of clindamycin combined with either gentamicin or colimycin was further demonstrated by following the kinetics of the bactericidal action of the antibiotic combinations and the effects on bacterial protein synthesis.
Disk Diffusion and Serial Dilution Tests of Susceptibility of Some Pathogenic Gram-Negative Bacilli and Enterococci to Carbenicillin and Ampicillin
Authors: Garner Carol , Rosner Bernard , Finland Maxwell
Published: June 2012

Tests for susceptibility to ampicillin and carbenicillin were performed with 35 strains each of
Klebsiella, Enterobacter, Serratia
, and
Proteus
, 71 strains of
Pseudomonas aeruginosa
, and 68 strains of enterococci by serial dilution and disk-diffusion tests employing 10
−3
dilutions of overnight cultures as inocula for both. Commercial 10-μg ampicillin and 50- and 100-μg carbenicillin disks, and freshly prepared 10-, 50-, and 75-μg ampicillin and 10- and 50-μg carbenicillin disks were used. Results were displayed as cumulative distribution curves for both minimal inhibitory concentrations and zone diameters, and as scattergrams for correlating them. Differences in susceptibility to the two antibiotics were small for
Klebsiella, Enterobacter
, and
Serratia
and large for the others. The freshly prepared and commercial disks of the same content gave comparable zones. There was good correlation of zone diameter with each disk and the minimal inhibitory concentration. Among the ampicillin disks tested, none was useful for
Pseudomonas
; with the other species, the 10-μg disk, as well as those with higher ampicillin content, could discriminate susceptible from resistant strains. However, only the 75-μg disk selected some
Klebsiella
strains susceptible to high concentrations. The 50- and 100-μg carbenicillin disks were equally discriminating for most strains, but the higher concentration was more selective for
Klebsiella
. The 10-μg carbenicillin disk was as effective as the 50- and 100-μg disks for discriminating among
Enterobacter, Serratia, Pseudomonas
, and
Proteus
, but not for
Klebsiella
or enterococci. The 10
−3
inoculum gave zone sizes considerably larger than those reported by other workers who used the standard Kirby-Bauer method.
Properties of the Gentamicin Acetyltransferase Enzyme and Application to the Assay of Aminoglycoside Antibiotics
Authors: Broughall J. M. , Reeves D. S.
Published: June 2012

The acetyltransferase technique of serum gentamicin assay was demonstrated to be specific for aminoglycoside antibiotics. The enzyme involved was isolated and stabilized by lyophilization.
In Vitro Evaluation of BL-S640 Cephalosporin Antibiotic
Authors: Overturf Gary D. , Ressler Ronald L. , Marengo Paul B. , Wilkins Jeanette
Published: June 2012

BL-S640, a new oral cephalosporin analogue, was evaluated in vitro against 102 gram-negative and 80 gram-positive bacteria. The antimicrobial spectrum was similar to that of previous cephalosporin analogues. Good antimicrobial activity against strains of
Escherichia coli, Klebsiella
, staphylococci, and streptococci was demonstrated. Relatively poor activity and/or resistance was noted among most strains of
Proteus, Providencia, Pseudomonas
, and
Serratia
. In comparative studies BL-S640 had better activity against strains of
Hemophilus influenzae, Staphylococcus aureus
, and
Enterobacteriaceae
than many cephalosporin analogues. Variation of susceptibility results was dependent upon the type of media and inoculum size. Cross-resistance between BL-S640 cephalexin, cephalothin, and cefazolin was demonstrated. Among strains of
Klebsiella
the more rapid selection of resistance ot other cephalosporins was in contrast to BL-S640. Experience in vitro with BL-S640 has documented its antimicrobial activity,and further studies of pharmacokinetics and therapeutic efficacy are indicated.
Relationship of Early Readings of Minimal Inhibitory Concentrations to the Results of Overnight Tests
Authors: Lampe Mary F. , Aitken Connie L. , Dennis Patricia G. , Forsythe Patricia S. , Patrick Kathryn E. , Schoenknecht Fritz D. , Sherris John C.
Published: June 2012

Broth dilution minimal inhibitory concentration (MIC) readings were compared after different incubation periods and with different inoculum concentrations. The purpose was to determine the best conditions for obtaining early results as close as possible to overnight readings. Initially, 76 antibiotic-organism combinations were tested using the International Collaborative Study technique and inoculum and were read after 3, 8, and 18 h of incubation. Approximately 28% of tests showed fourfold or greater increases in MICs after 18 h of incubation compared with the 3-h readings. No overnight MICs were lower than early readings. MICs of single antibiotics against seven organisms were also read with an automatic particle counter to confirm the validity of the visual readings. Experiments were made to determine whether inoculum manipulation could reconcile the differences between 3- and 18-h MIC results. One hundred and eight organism-antibiotic combinations were tested comparing 3-h MIC readings using an inoculum of 10
7
organisms per ml with overnight readings using 10
5
per ml. In 71 cases, readings with both inocula were within the range tested and 57 (86%) were within ±1 log
2
of each other and followed an approximately normal distribution. Improved comparability between early read and overnight MICs thus may be achieved by inoculum manipulation, and this may be a suitable approach in the future development of automated procedures.
Virulence in Rats of Gentamicin-Carbenicillin-Resistant
Pseudomonas
Authors: Slepack Jerry M. , Korfhagen Thomas , Loper John C. , Tan James S. , Phair John P.
Published: June 2012

Strains of
Pseudomonas aeruginosa
, with resistance to gentamicin and carbenicillin which is R factor mediated, showed no alteration in virulence as tested by intraperitoneal injection of rats.
Human Therapeutic and Agricultural Uses of Antibacterial Drugs and Resistance of the Enteric Flora of Humans
Authors: Siegel D. , Huber W. G. , Drysdale S.
Published: June 2012

Fecal samples were collected from five groups of people differing in the manner of their exposure to antibacterial drugs. The groups included: (i) people working on farms who were continuously in contact with the predominantly resistant florae of farm animals receiving rations containing antibacterial drugs, (ii) people residing on the same farms with no direct exposure to the farm animals, (iii) people treated with antibacterial drugs, (iv) untreated people residing with treated individuals, and (v) untreated people with no exposure to farm animals or treated individuals. The samples were examined by quantitative plating for proportions of antibiotic-resistant, gram-negative enteric organisms. Individual isolates were also examined for their susceptibility to 11 different antibacterial drugs. The results indicate that enteric florae unexposed directly to the selective effects of antibacterial drugs may be affected by contact with predominantly resistant florae directly exposed to antibacterial drugs.
Treatment of Respiratory
Klebsiella pneumoniae
Infection in Mice with Aerosols of Kanamycin
Authors: Berendt R. F. , Long G. G. , Walker J. S.
Published: June 2012

Aerosols of kanamycin resulted in greater survival of mice challenged with respiratory
Klebsiella pneumoniae
than the same dosage given intramuscularly. Determinations of viable bacteria in the blood and lungs revealed that aerosolized kanamycin was most effective when infection was confined to the lungs. After the organisms had spread to other areas, however, aerosol therapy was still more effective than intramuscular therapy, but only one-half the infected mice survived.
Prevention of Herpes Keratoconjunctivitis in Rabbits By Silver Sulfadiazine
Authors: Chang Te-Wen , Weinstein Louis
Published: June 2012

Silver sulfadiazine, at a concentration of 10 μg/ml when applied immediately after infection by
Herpesvirus hominis
, prevented the development of acute herpetic keratoconjunctivitis in rabbits. The efficacy was inversely related to the size of inoculum. Subclinical infections were observed in the drug-treated eyes.
Susceptibility of
Mycobacterium leprae
to Dapsone as a Determinant of Patient Response to Acedapsone
Authors: Levy Louis , Peters John H.
Published: June 2012

In the course of a clinical trial of acedapsone therapy in 17 patients with lepromatous leprosy, the rate of response to therapy was measured by inoculation of mice with
Mycobacterium leprae
recovered from biopsy specimens of skin lesions obtained before treatment and at intervals of 4, 12, and 24 weeks after institution of treatment. The susceptibility of each isolate of
M. leprae
to dapsone (4,4′-diaminodiphenylsulfone [DDS]) was measured by passaging organisms that had multiplied in mice to new groups of untreated mice and to mice treated with DDS incorporated in the mouse chow in concentrations of 10
−5
, 3 × 10
−5
, and 10
−4
g/100 ml. The rate of response to acedapsone therapy and the susceptibility of patient strains of
M. leprae
to DDS varied widely among patients. All isolates were inhibited from multiplication by treatment of mice with 10
−4
g of DDS per 100 ml; all but two isolates were susceptible to 3 × 10
−5
g of DDS per 100 ml; and 17 of 36 isolates, representing nine patient strains, were susceptible to 10
−5
g of DDS per 100 ml. Plasma levels of DDS measured in the mice administered these diets show that the minimal inhibitory concentration of DDS for
M. leprae
isolated from untreated patients is about 3 ng/ml. No relationship could be demonstrated between DDS susceptibility of pretreatment isolates of
M. leprae
and the rate at which patients responded to acedapsone therapy. Neither acedapsone treatment of patients nor DDS treatment of mice appeared to select genotypically more resistant
M. leprae
.
Pharmacological Studies with Cefamandole in Human Volunteers
Authors: Meyers Burt R. , Ribner Bruce , Yancovitz Stanley , Hirschman Shalom Z.
Published: June 2012

Serum and urine concentrations were measured after administration of 0.5-and 1-g doses of cefamandole intramuscularly and intravenously to healthy volunteers. Intramuscular doses of 0.5 and 1 g yielded serum concentrations at 1 h of 14.7 and 35.6 μg/ml, respectively. Significant antibacterial concentrations persisted through h 8. Intravenous doses of 0.5 and 1 g resulted in respective peak serum levels of 21 μg/ml at 45 min and 103 μg/ml at 15 min; these serum levels rapidly declined. Very high urine concentrations were achieved during the first 8 h after injection.
Viridins, Bacteriocins of Alpha-Hemolytic Streptococci: Isolation, Characterization, and Partial Purification
Authors: Dajani Adnan S. , Tom May C. , Law David J.
Published: June 2012

Bacteriocin-like activities were detected in 78% of 120 alpha-hemolytic streptococcal isolates. Inhibitory substances from three such isolates (one
Streptococcus sanguis
strain and two
S. mitis
strains) were investigated further and termed viridins (A, B, and C). The viridins were unique among bacteriocins of gram-positive bacteria in that they inhibited many gram-negative bacteria in addition to inhibition of a variety of gram-positive organisms. Viridins were obtained in a cell-free state only after mechanical disruption of bacteriocinogenic cells but could not be isolated from supernatant fluids of cultures of such bacteria or from freeze-thaw liquor of agar on which the bacteria had been grown. Viridin B could be partially purified by ammonium sulfate precipitation and by gel filtration on a Sephadex G-100 column. This bacteriocin had some unusual properties including heat lability, a narrow pH range of activity, and lack of adsorptive capacity to susceptible bacteria. Although viridin B was bactericidal to a
Neisseria sicca
strain, it was only bacteriostatic against a coagulase-negative staphylococcus.
Clinical and Pharmacological Studies of Ticarcillin in Gram-Negative Infections
Authors: Ervin F. Richard , Bullock Ward E.
Published: June 2012

Twenty-seven patients with serious gram-negative infections were treated with ticarcillin in an average daily dosage of 237 mg/kg (range, 174 to 307 mg/kg). Ticarcillin was bactericidal for all infecting organisms in concentrations ranging from 31.2 to 125 μg/ml. Five of 8 patients (62%) with overwhelming
Pseudomonas
pneumonia were cured or improved, and 9 of 12 (75%) were cured of pneumonia caused by other gram-negative organisms. Of six extrapulmonary infections caused by
Pseudomonas
, five (83%) were cured or improved. In seven cases, the infecting organism reisolated during therapy was more resistant to ticarcillin than the primary isolate. The serum half-life of ticarcillin in three patients with renal failure was 11.2 ± 1.0 h, and during hemodialysis it decreased to 6.3 ± 1.8 h. There were two episodes of superinfection with resistant organisms. Thirteen patients (48%) manifested eosinophilia, one of whom had severe urticaria. Prolongation of bleeding time was attributable to ticarcillin in two patients. Ticarcillin appears to be effective for therapy of serious gram-negative infections in dosages 30 to 50% less than those recommended for carbenicillin.
Trimethoprim-Sulfamethoxazole in Murine Toxoplasmosis
Authors: Remington Jack S.
Published: June 2012

The combination trimethoprim-sulfamethoxazole had no greater activity in a murine model of toxoplasmosis than did sulfamethoxazole alone.
Radioimmunoassay of Sisomicin
Authors: Broughton Alan , Strong James E. , Bodey Gerald P.
Published: June 2012

An antibody induced in rabbits against a gentamicin-bovine serum albumin conjugate cross-reacted with the chemically related aminoglycoside, sisomicin, facilitating the development of a sisomicin radioimmunoassay. Sisomicin was labeled with
125
I using an acylating agent [3-(4-hydroxyphenyl)propionic acid-
N
-hydroxy-succinimide ester]. The resulting assay produced a linear standard curve on a logit-log plot with a sensitivity of 140 pg. Comparison with a microbiological assay showed no significant difference (
P
< 0.001) in the measurement of sisomicin by these two methods.
Susceptibility of Pneumococci and
Haemophilus influenzae
to Antibacterial Agents
Authors: Finland Maxwell , Garner Carol , Wilcox Clare , Sabath Leon D.
Published: June 2012

Strains of
Diplococcus pneumoniae
and
Haemophilus influenzae
were tested for susceptibility to numerous antibiotics by a twofold agar dilution method using an inocula replicator. Undiluted, fully grown broth cultures were used as inocula for both species, and cultures of pneumococci diluted 1:1,000 were also tested. The antibiotics included most of those in common use in the United States as well as some chemical modifications recently approved and others that are under investigation. The most striking aspect of the results was the marked susceptibility of the pneumococci to all the antibiotics tested except the polymyxins and most of the aminoglycoside antibiotics, although some new aminoglycosides were active in quite low concentrations. Some of the strains of pneumococci were of decreased susceptibility to penicillin G (minimal inhibitory concentrations, 0.2 to 0.4 μg/ml), but none were tetracycline resistant, although such strains had been reported previously from this laboratory. The strains of
H. influenzae
, which were all serologically nontypable, exhibited different patterns of susceptibility to the groups of antibiotics and to the individual chemically related ones. None of these strains (isolated early in 1972) were ampicillin resistant. The most active agents against
H. influenzae
were: carbenicillin and ampicillin, analogues related to each of them, rifampin, chloramphenicol, and the polymyxins. However, the tetracycline analogues other than tetracycline, some aminoglycosides, notably tobramycin, kanamycin, gentamicin, and verdamicin, erythromycin, and some new lincomycin analogues were also active in low concentrations. Trimethoprim alone was highly active, and in combination with sulfamethoxazole it was even more active and synergistic against strains of both
D. pneumoniae
and
H. influenzae
.
Novel Mechanism of Resistance to Folate Analogues: Ribonucleoside Diphosphate Reductase Deficiency in Bacteriophage T4
Authors: Johnson James Robert , Collins Gerard M. , Rementer Marcia L. , Hall Dwight H.
Published: June 2012

Some spontaneously occurring bacteriophage T4 mutants (
far
mutants) were able to form plaques in the presence of concentrations of folate analogues that completely inhibit plaque formation by wild-type phage T4. Some of these
far
mutants were shown to be ribonucleoside diphosphate (RDP) reductase (EC 1.17.4.1) deficient, and some independently isolated RDP reductase-deficient mutants (
nrd
mutants) were shown to be folate analogue resistant. The map positions of the RDP reductase-deficient
far
mutants were shown to be within the genes controlling the phage-induced RDP reductase activity.
Suppressive Activity of Mefloquine in Sporozoite-Induced Human Malaria
Authors: Clyde David F. , McCarthy Vincent C. , Miller Roger M. , Hornick Richard B.
Published: June 2012

Mefloquine hydrochloride [WR 142,490; α-(2-piperidyl)-2,8-bis(trifluoromethyl)-4-quinolinemethanol hydrochloride] was tested for suppressive effect on sporozoite-induced malaria in nonimmune volunteers living in an area where malaria is not naturally transmitted. Single doses of 250 mg were given at weekly intervals, 500 mg at intervals of 2 weeks and 1,000 mg at intervals of 4 weeks, to men bitten by 10 to 15 mosquitoes heavily infected with a chloroquine- and pyrimethamine-resistant strain of
Plasmodium falciparum
. None of the individuals so treated developed infections during the period of drug delivery or during the follow-up period of 60 days. Doses of 250 or 500 mg produced no adverse reactions; mild epigastric discomfort occurred in all three men given 1,000 mg. Sporozoite-induced
P. vivax
infections were suppressed by single doses of 250 mg of mefloquine given at weekly intervals, but malaria developed after completion of the course. At treatment intervals longer than 1 week, vivax malaria was not suppressed.
Stimulation of Murine Interferon by a Substituted Pyrimidine
Authors: Nichol F. R. , Weed S. D. , Underwood G. E.
Published: June 2012

2-Amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166) induced high levels of circulating interferon in mice when administered either parenterally or orally. Peak titers of interferon were found in the serum between 6 and 12 h after inoculation of the drug. Lower but significant levels of interferon were found in rat serum after administration of U-25,166 by either the intraperitoneal or oral route, and good levels of circulating interferon were observed in cats after oral treatment. Repeated intraperitoneal doses (50 mg/kg) of U-25,166 protected mice against intranasal encephalomyocarditis virus challenge. The minimal effective acute oral dose for antiviral activity was approximately 250 mg/kg. This was also the minimal dose that produced detectable levels of interferon. Maximum tolerated doses in mice were four to six times the minimal effective doses. A single oral treatment was protective in mice against challenge virus inoculated 24 h later. The compound protected mice from challenge with high levels of encephalomyocarditis virus, up to 20,000 mean lethal doses. Antiviral activity in mice was retained when certain minor substitutions were made in the U-25,166 structure.
Immunosuppressant Activity of the Ansamycins
Authors: Kasik J. E. , Monick M. , Thompson J. S.
Published: June 2012

The immunosuppressive effect of four analogues of rifampin and two streptovaracins on cell-mediated immunity has been determined. Tuberculin hypersensitivity in the footpads of immunized mice was inhibited by three of the rifampin analogues and by both streptovaracins. The observed in vivo immunosuppressive activity of the compounds tested was not correlated with their in vitro activity against mycobacterial growth but was associated with their toxicity in mice. These data indicate that some of the analogues of rifampin and the streptovaracins can significantly suppress cell-mediated immunity and suggest that other ansamycins may have significant immunosuppressant activity.
Comparison of the Binding of Penicillin G to Staphylococcal L-Form and Its Parent Strain Membranes
Authors: Suginaka Hidekazu
Published: June 2012

The binding of penicillin G to a stable L-form from
Staphylococcus aureus
followed saturation-type kinetics with saturation achieved at 0.75 nmol/ml, the same as with its parent strain.
Comparative Incidence of Phlebitis Due to Buffered Cephalothin, Cephapirin, and Cefamandole
Authors: Berger Stephen , Ernst E. Chaim , Barza Michael
Published: June 2012

Buffered cephalothin, cefamandole, and cephapirin were compared with respect to their tendency to produce phlebitis. Two grams of each agent was administered every 6 h for 4 days to 12 healthy volunteers in a double-blind crossover fashion. Approximately 50% of intravenous sites developed mild (grade 1) phlebitis and 25% developed moderate (grade 2) phlebitis. The frequency of grade 1 inflammation did not differ significantly among the three cephalosporins. The proportion of individuals eventually exhibiting grade 2 phelebitis was highest with cefamandole, lowest with cephalothin (
P
= 0.07), and intermediate with cephapirin; however, cephapirin required a substantially greater number of doses to produce grade 2 phelebitis than did the other two drugs. These findings, together with the results of other reports, suggest that interpretation of the phlebitogenic potential of these antibiotics must be made with caution.
Pirbenicillin, a New Semisynthetic Penicillin with Broad-Spectrum Activity
Authors: Bodey Gerald P. , Rodriguez Victorio , Weaver Suzanne
Published: June 2012

Pirbenicillin is a new semisynthetic penicillin which inhibited 67% of isolates of
Proteus aeruginosa
tested in our laboratory, 93% of
P. mirabilis
, 31% of
Enterobacter
spp., 41% of
Serratia
spp., and 58% of
Escherichia coli
at a concentration of 6.25 μg/ml. Its activity appeared to be inoculum dependent and it was virtually inactive against 10
7
inocula of
P. aeruginosa
. It was more active than carbenicillin or ticarcillin, but less active than BL-P1654 against
P. aeruginosa
. Carbenicillin and ticarcillin appeared to be more active than pirbenicillin against
Proteus
spp., but pirbenicillin was active against some isolates of
Klebsiella
spp.
Increased Antibiotic Resistance of
Neisseria gonorrhoeae
in Korea
Authors: Wilson Clarence , Rose David L. , Tramont Edmund C.
Published: June 2012

There has been a marked increase in the resistance of
Neisseria gonorrhoeae
isolated in Korea to penicillin, ampicillin, and tetracycline. In contrast, there has been no increased resistance to spectinomycin.
Comparison of Phlebitis Produced by Cephapirin and Cephalothin
Authors: Cross Alan S. , Tramont Edmund C.
Published: June 2012

In a single-blinded study involving 120 patients neither the incidence nor severity of phlebitis observed with cephapirin and cephalothin was significantly different.
Susceptibility and Resistance of
Candida
to 5-Fluorocytosine in Relation to the Cell Wall Ultrastructure
Authors: Montplaisir Serge , Nabarra Bernadette , Drouhet Edouard
Published: June 2012

Studies on the susceptibility of
Candida albicans
to 5-fluorocytosine (5FC) demonstrated a high rate of resistance (85%) for serogroup B strains, more frequently isolated in Africa, and a low incidence (<1%) for serogroup A, predominating among Whites (Drouhet et al., 1974). Determination of the electrophoretic mobility of various strains did not provide a correlation between the charged groups of the surface and their phenotype to 5FC and antigenic groups. Adsorption of the surface antigens with a hyperimmune antiserum did not modify the phenotypic expression of
Candida
to 5FC. Electron microscopy studies revealed that susceptible strains had an additional granular layer dividing the inner stratum into two parts. After trypsin digestion of these strains, the disappearance of this layer was concomitantly associated with the emergence of resistance. Thus, it appears that the cell wall contains a proteinic material, which is located in the interior of the electron-transparent region and acts in the metabolism of 5FC.
Impregnated Disk Method for Antifungal Antibiotic Testing
Authors: Boyer Jere M.
Published: June 2012

Sixteen clinical fungal isolates were tested for antibiotic susceptibility by using disks impregnated with growth medium and antibiotic. The procedure was easier to perform, less time consuming, and as reliable as other currently available methods.
Antibiotic Action of
Solanum incanum
Linnaeus
Authors: Beaman-Mbaya V. , Muhammed S. I.
Published: June 2012

The fruits of
Solanum incanum
Linnaeus are extensively used in Kenya for the treatment of cutaneous mycotic infections and other pathological conditions. The therapeutic activity of the berries has been attributed to their content of solanine and related glycoalkaloids, which are saponins and cytostatic poisons. In the present study, however, a simpler more potent antimicrobial substance with a phosphorylated structure similar to the purine adenine was isolated from the berries. The crystals of this compound were effective inhibitors of the growth of gram-positive and -negative bacteria, yeasts, dermatophytes, and some pathogens of agricultural produce. High concentrations of the substance caused hemolysis of erythrocytes.