bluuebunny/crossref_metadata_2025 huggingface dataset:
Unusual Susceptibility of
Erwinia amylovora
to Antibacterial Agents in Relation to the Barrier Function of its Cell Envelope
Authors: Chatterjee Arun K. , Buss Richard F. , Starr Mortimer P.
Published: June 2012

Wild-type strains of the bacterial phytopathogen
Erwinia amylovora
(the cause of fire blight disease of apples and pears) are markedly susceptible to novobiocin, deoxycholate, and sodium dodecyl (= lauryl) sulfate. The inhibitory concentration, expressed as the concentration causing a 99% inhibition of growth, of these three antibacterial agents were 15 to 100, 40 to 800, and 50 to 800 μg/ml, respectively, depending on the
E. amylovora
strain. Growth of strains of other
Erwinia
spp. and
Salmonella typhimurium
is not affected at all, or is only slightly affected, at these concentrations. Introduction of the F′
lac
+
, RP1, and R100
drd
-56 (but not E-
lac
+
) plasmids into an
E. amylovora
strain results in enhanced susceptibility to novobiocin and sodium dodecyl sulfate but not to deoxycholate.
E. amylovora
wild-type strains spontaneously release a periplasmic enzyme, cyclic phosphodiesterase, but not a cytoplasmic enzyme, glucose-6-phosphate dehydrogenase, into the growth medium. Addition of MgCl
2
(20 mM) and NaCl (84 mM) to tryptone broth stimulates the growth of wild-type
E. amylovora
strains and reduces or eliminates leakage of the periplasmic enzyme. Mutant strains of
E. amylovora
, selected for resistance to each separate antibacterial agent (or to all three of them), showed a direct correlation (in all but the novobiocin-resistant mutant) between drug resistance and reduced periplasmic leakiness. The relatively low maximum growth temperature (<37°C) of
E. amylovora
seems unrelated to periplasmic leakage, as judged from the inability of added MgCl
2
to raise the maximum growth temperature, although the generation time at 30°C is reduced from 108 to 54 min upon the addition of 20 mM MgCl
2
. The extensive leakage of periplasmic enzyme and unusual drug susceptibility of
E. amylovora
strains might stem from some defect(s) in some cell envelope component(s) other than the lipopolysaccharide of these bacteria (which contain the usual liposaccharide constituents).
In Vitro Synergism Between Carbenicillin and Aminoglycosidic Aminocyclitols Against
Acinetobacter calcoaceticus
var.
anitratus
Authors: Glew Richard H. , Moellering Robert C. , Buettner Karen R.
Published: June 2012

Acinetobacter caleoaceticus
var.
anitratus
is a nonfermentative, gram-negative bacillus that has been demonstrated to cause severe infections, usually in hospitalized patients. Since mild to moderate resistance of
A. calcoaceticus
to one or more aminoglycosidic aminocyclitols has been noted to occur, a study was undertaken to evaluate the activity of combinations of carbenicillin with either kanamycin, tobramycin, or gentamicin against 28 isolates of
A. calcoaceticus
obtained from clinical sources. Synergism (defined as at least 100-fold-increased killing at 24 h by the combination as compared with the most efficacious of the individual antibiotics) was demonstrated against 26 of 28 strains of
A. calcoaceticus
with carbenicillin plus kanamycin and carbenicillin plus tobramycin and against 25 of 28 strains with carbenicillin plus gentamicin. The median increased killing for the 28 strains was 4.2 log
10
with carbenicillin plus kanamycin and with carbenicillin plus tobramycin and 3.1 log
10
with carbenicillin plus gentamicin. The most important determinant of synergistic potential of each combination was the level of resistance of each strain of
A. calcoaceticus
to the aminoglycoside component of the combination.
Distribution of Gentamicin and Amikacin in Rabbit Tissues
Authors: Kornguth Margaret L. , Kunin Calvin M.
Published: June 2012

Rabbits were injected intramuscularly with gentamicin and amikacin (15 mg of base per kg), and the antibiotic levels in tissues were determined 20 h after either a single or multiple injections. Disk diffusion assays, with
Bacillus subtilis
ATCC 6633, were carried out both on homogenates and on supernatants deproteinized with trichloroacetic acid. Both assays indicated that the kidney is the major site of antibiotic deposition. Antibiotic levels increased after multiple doses. Gentamicin levels in other tissues were higher than those of amikacin. The assay of trichloroacetic acid-treated material was more sensitive than the assay of the total homogenate.
Altered Surface Properties of
Escherichia coli
Associated With a Specific Amino Acid Change in the S12 Ribosomal Protein of Streptomycin-Resistant Mutants
Authors: Pestka Sidney , Walter Harry , Wayne Lawrence G.
Published: June 2012

Escherichia coli
mutants resistant to streptomycin exhibited differences in countercurrent distribution from the parental strains. The degree of difference from the parental strain correlated with the degree of restriction of translation and thus the particular
strA
allele. The changes in countercurrent distribution in the phase systems used probably resulted predominantly from surface charge alterations. The differences in countercurrent distribution in these and other mutants may be a useful selective technique to obtain different types of mutants for which specific selective techniques may not be available. In addition, it appears that the surface properties of cells, which determine their position in countercurrent distribution, are a function of the translational efficiency and fidelity, and that the surface of cells consists of a mosaic that is an expression of this translational fidelity.
Human Interferon: Mass Production in a Newly Established Cell Line, MG-63
Authors: Billiau A. , Edy V. G. , Heremans Hubertine , Van Damme J. , Desmyter J. , Georgiades J. A. , De Somer P.
Published: June 2012

MG-63 cells, a line derived from an osteosarcoma, produced high yields of interferon after superinduction with polyinosinic acid·polycytidylic acid, cycloheximide, and actinomycin D. Advantages of MG-63 cells over diploid fibroblasts as a substrate are: no requirement for aging between confluency and induction, no requirement for priming, and 3.7-fold higher yields per square centimeter of culture surface. Physicochemically and biologically, MG-63 cell interferon resembles fibroblast rather than leukocyte interferon.
In Vitro Activity of
p
-Hydroxybenzyl Penicillin (Penicillin X) and Five Other Penicillins Against
Neisseria gonorrhoeae
: Comparisons of Strains from Patients with Uncomplicated Infections and from Women with Pelvic Inflammatory Disease
Authors: Sackel Stephen G. , Alpert Susan , Rosner Bernard , McCormack William M. , Finland Maxwell
Published: June 2012

Minimum inhibitory concentrations (MICs) of six penicillins against 95 strains of
Neisseria gonorrhoeae
from patients with uncomplicated anogenital infections and 22 strains from women with pelvic inflammatory disease were determined by an agar plate dilution method, using an inocula replicator. Against all 117 strains, the order of activity observed was: BL-P1654 > penicillin X > penicillin G > ampicillin > amoxicillin = carbenicillin. MICs against strains isolated from women with gonococcal pelvic inflammatory disease were significantly higher than those against isolates from uncomplicated infections: BL-P1654,
P
< 0.001; penicillin X,
P
< 0.001; penicillin G,
P
< 0.001; ampicillin,
P
< 0.001; and amoxicillin,
P
< 0.05. MICs of penicillin G were ≥0.125 μg/ml against 33 (36%) of the 92 strains from patients with uncomplicated infections, as contrasted with 15 (68%) of the 22 isolates from women with pelvic inflammatory disease (
P
< 0.01). The means of the MICs of penicillin G were 0.06 μg/ml for the former and 0.14 μg/ml for the latter.
Susceptibility to Kasugamycin of
Escherichia coli
Carrying Conjugative and Nonconjugative R Plasmids
Authors: Danbara Hirofumi , Yoshikawa Masanosuke
Published: June 2012

Ten conjugative and two nonconjugative R plasmids, all of which were naturally isolated, were tested for their ability to confer epistatic susceptibility to kasugamycin upon the host
Escherichia coli
. All of the conjugative plasmids, which belonged to various incompatibility groups, conferred a plasmid-determined epistatic susceptibility to kasugamycin upon the host cells, whereas the nonconjugative plasmids did not.
Spread of a Single Plasmid Clone to an Untreated Individual from a Person Receiving Prolonged Tetracycline Therapy
Authors: Petrocheilou V. , Richmond M. H. , Bennett P. M.
Published: June 2012

The aerobic gram-negative intestinal flora of two individuals living in close proximity was followed for 17 months. One of these persons was receiving a prolonged tetracycline treatment for acne vulgaris and was colonized by tetracycline-resistant
Escherichia coli
strains throughout the survey. The other person studied received no antibiotics during the period in question, but was frequently found to excrete a number of
E. coli
strains harboring tetracycline-resistant plasmids. The two
E. coli
strains (O75.H7 and O23.H16) excreted from both persons most frequently were indistinguishable, and so were the R-plasmids they carried. This suggests that R-plasmid-carrying
E. coli
may spread from individuals under treatment to close relatives that have not been treated.
Simple Method for Elimination of Aminoglycosides from Serum to Permit Bioassay of Other Antimicrobial Agents
Authors: Stevens Paul , Young Lowell S.
Published: June 2012

Cellulose phosphate powder can be added to serum to selectively bind aminoglycosides by ionic interaction without binding or inactivation of the penicillins, the cephalosporins, clindamycin, vancomycin, chloramphenicol, or trimethoprim. This simple, rapid technique permits the measurement of non-aminoglycoside antibiotics in the presence of aminoglycosides.
Correlation of Netilmicin Agar Dilution and Disk Diffusion Susceptibilities
Authors: Goldmann Donald A. , Syriopoulou Georgia Ph. , Semple Anne Markley
Published: June 2012

A study of 283 isolates of gram-negative bacilli revealed a good correlation (
r
= −0.74) between disk diffusion zones of inhibition and agar dilution minimal inhibitory concentrations. Regression analysis suggested that strains with zone sizes 11 mm should be considered resistant, but 34 of 45 strains resistant by minimal inhibitory concentration (including 27 strains of
Pseudomonas aeruginosa
) would have been called susceptible using this break point.
Sensitive, Rapid, and Specific Bioassay for the Determination of Antilipogenic Compounds
Authors: Ulitzur S. , Goldberg I.
Published: June 2012

A sensitive and rapid bioassay for the determination of the antilipogenic compounds cerulenin and CM-55 is described. The bioassay is based on the inhibitory effect of cerulenin and CM-55 on the in vivo luminescence of an aldehyde-requiring mutant of the marine bacterium
Beneckea harveyi
. A total quantity as low as 0.1 μg of cerulenin can be determined within 15 min with an error of ±2%. The bioassay, as presented, is specific for compounds that are known to inhibit fatty acid biosynthesis and, as such, it might be used as a general screening method for the detection of antilipogenic compounds.
Netilmicin Pharmacokinetics After Single Intravenous Doses to Elderly Male Patients
Authors: Welling Peter G. , Baumueller Axel , Lau Curtis C. , Madsen Paul O.
Published: June 2012

The pharmacokinetics of the new aminoglycoside antibiotic netilmicin were examined after single intravenous injections at two different dose levels to elderly male patients. The durg obeyed two-compartment model kinetics in serum, and elimination was monoexponential from 1 to 2 h after dosing. Netilmicin levels in serum were above minimum inhibitory concentration values for most susceptible organisms for up to 8 h after dosing in normal individuals and for at least 12 h in uremic patients. Urine levels of netilmicin were uniformly above minimum inhibitory concentration values throughout 24 h after dosing. Netilmicin distribution characteristics were largely independent of both dose level and renal function. Netilmicin elimination kinetics were independent of dose level but were markedly influenced by renal function. Relationships are described between netilmicin elimination and renal function indicators, which provide a basis for dosage adjustment in individuals with renal function impairment.
Biotransformation of Sisomicin to Gentamicin C
2b
Authors: Lee B. K. , Bailey J. V. , Condon R. G. , Marquez J. A. , Wagman G. H. , Weinstein M. J.
Published: June 2012

Sisomicin was transformed to gentamicin C
2b
by
Micromonospora rhodorangea
NRRL 5326. The mechanisms involved in the biotransformation are the 6′-
N
-methylation and the (4′-5′)-reduction. The progression of the methylation was followed by the isotope technique, but the reduction reaction was not monitored.
Bacteriolytic Action of Fluoride Ions
Authors: Lesher Robert J. , Bender Gary R. , Marquis Robert E.
Published: June 2012

Bacillus subtilis, Neisseria subflava
, and LYT coccus were found to undergo massive lysis after growth in media containing 0.01 to 10 mM NaF. When cells of these organisms were transferred from late-exponential-phase cultures to 0.02 M sodium phosphate buffer plus 0.1 M KCl, they underwent spontaneous autolysis. Cells grown in media with fluoride were more liable to autolysis, and walls isolated from them also showed enhanced autolytic sensitivity, even though added fluoride did not directly stimulate autolysins. Sporadic or partial lysis occurred in populations of
Streptococcus sanguis
and
Streptococcus mutans
BHT or LM-7 after growth in fluoridated media. Most bacteria that were tested did not undergo fluoride-induced lysis. However, cells of all test bacteria were found to have reduced amounts of peptidoglycan per unit of cell weight when grown in the presence of fluoride. Incorporation of labeled lysine or glucosamine into peptidoglycan (Park-Hancock residue) was stimulated, instead of inhibited, by fluoride. However, fluoride also stimulated the loss of radioactivity from Park-Hancock residues of cells that had previously incorporated labeled lysine or glucosamine. Thus, fluoride appeared to enhance peptidoglycan turnover, and this turnover reduced the peptidoglycan contents of all bacteria tested, but induced lysis in only those bacteria that normally have highly active autolytic systems.
Drug Resistance in
Streptococcus pyogenes
Isolated in Japan (1974–1975)
Authors: Nakae Masataka , Murai Teiko , Kaneko Yoshinori , Mitsuhashi Susumu
Published: June 2012

Drug resistance of
Streptococcus pyogenes
strains isolated during 1974 and 1975 in various districts in Japan were surveyed and compared with an earlier survey of 1970 to 1973. Of 1,021 strains, tetracycline-, macrolide antibiotic-, lincomycin-, and chloramphenicol-resistant strains were demonstrated at frequencies of 80.3, 62.3, 60.8, and 57.9%, respectively. Distinct group resistances to penicillin and aminoglycoside antibiotics could not be identified among the strains examined. It was characteristic that quadruple and triple resistances were manifested among the strains resistant to macrolide antibiotics, lincomycin, tetracycline, and chloramphenicol, and they were confined to the T-type 12. The emergence of multiply resistant streptococcal strains was due mostly to the rapid increase in isolation frequency of macrolide antibiotic- or macrolide antibiotics–lincomycin-resistant strains.
Methicillin Hemorrhagic Cystitis
Authors: Bracis R. , Sanders C. V. , Gilbert D. N.
Published: June 2012

Interstitial nephritis is a recognized complication of methicillin therapy. Hemorrhagic cystitis due to methicillin has not been emphasized. Evidence of hemorrhagic cystitis developed in six patients receiving methicillin therapy and was confirmed by cystoscopy in three of them.
Latent Herpes Simplex Virus Infections in Sensory Ganglia of Mice After Topical Treatment with Adenine Arabinoside and Adenine Arabinoside Monophosphate
Authors: Klein Richard J. , Friedman-Kien Alvin E.
Published: June 2012

Adenine arabinoside (Ara-A) and Ara-A monosphosphate (Ara-AMP) ointments were able to prevent the fatal outcome of herpes simplex virus (HSV)-induced skin infection of the lumbosacral area in hairless mice. Ara-A and Ara-AMP had no irritating effect on the skin, but in a number of animals a protracted healing time of the skin lesions after the treatment was observed. The compounds conferred only a partial protection against the establishment of latent HSV infection in the spinal root ganglia of the treated animals. The immune response, as judged from levels of HSV-specific neutralizing serum antibody titers, was not impaired by the antiviral treatment.
Inhibition of Acetylating Activity in an Enzymatic Assay for Aminoglycoside Antibiotics
Authors: Minshew Barbara H. , Swanzy Susan R. , Schoenknecht Fritz D.
Published: June 2012

The radioenzymatic technique using aminoglycoside-6′-acetyltransferase is suitable for determining serum concentrations of aminoglycoside antibiotics that have a 6′-amino group. Standard curves constructed for each drug in normal human serum are generally satisfactory, but we encountered a pool of human serum (designated IN pool) that inhibited the acetylating activity of the assay. Standard curves for amikacin, kanamycin, gentamicin, and tobramycin in the acetylating assay were all abnormal with standards prepared in the IN pool. Acetylating activity was also inhibited with amikacin standards prepared in a filtrate of this serum pool. Heat inactivation (56°C for 30 min) of the IN pool did not eliminate the problem. When the IN pool was diluted 1:10 in normal human serum, the standard curve obtained with amikacin was comparable to the curve with standards prepared in normal human serum. With amikacin standards prepared in a 1:2 dilution of the IN pool in normal human serum, an intermediate level of acetylating activity was observed. When this IN pool was used for the preparation of gentamicin and amikacin standards in a bioassay with
Klebsiella pneumoniae
ATCC 27799 as the test strain, valid standard curves and concentrations were obtained. Furthermore, no differences in the biological activity of amikacin were observed with
Pseudomonas aeruginosa
or
Bacillus subtilis
as the test strain. Excellent agreement between the microbial assay and the enzymatic assay was obtained with serum specimens tested for gentamicin (
r
= 0.89), tobramycin (
r
= 0.96), and amikacin (
r
= 0.96). The results obtained with the IN pool illustrate the need for regular use of check samples of known performance, independent from the standards, when determining antibiotic levels in serum.
Methadone: Antimicrobial Activity and Interaction with Antibiotics
Authors: Sheagren John N. , Barsoum Ibrahim S. , Lin Melody Y. C.
Published: June 2012

We studied the effect of methadone, alone and in combination with antimicrobial agents, on two strains each of
Staphylococcus aureus, Pseudomonas aeruginosa
, and
Serratia marcescens
isolated from blood streams of parenteral drug abusers with bacterial endocarditis. Methadone has its own antibacterial effect, although at supraphysiological concentrations, and is even synergistic with antimicrobial agents against some organisms. Thus, methadone does not interfere with the antibacterial effects of antibiotics in vitro.
Assay Conditions and the Demonstration of Nitroimidazole Resistance in
Tritrichomonas foetus
Authors: Meingassner Josef G. , Mieth Hubert , Czok Rudolf , Lindmark Donald G. , Müller Miklós
Published: June 2012

Tritrichomonas foetus
KV
1
, a nitroimidazole-susceptible strain, and KV
1
/M100, its nitroimidazole-resistant daughter strain, differed markedly in their in vivo susceptibility to metronidazole. In vitro susceptibility testing in multiwell plates and tubes with different trichomonad media containing no, or low concentrations of, ascorbate demonstrated that the resistant strain behaves like the susceptible one, if tested under anaerobic conditions (deep cultures in tubes or multiwell plates in anaerobic jars), but shows resistance if tested in the presence of air (multiwell plates exposed to air). In media containing high concentrations of ascorbate, no resistance was observed even in air. The results suggest that the two strains differ in the regulation of internal redox systems and underscore the role testing methods may play in the in vitro detection of nitroimidazole-resistant protozoan parasites.
Hemodialysis-Associated Infections: Treatment with Cephapirin
Authors: Berman S. J. , Boughton W. H. , Sugihara J. G. , Wong E. G. C. , Siemsen A. W.
Published: June 2012

Large doses of cephapirin (50 mg/kg) administered during the first and last half hours of routine hemodialysis produced effective antimicrobial serum concentrations for 48 h. Repetitive administration during five successive hemodialysis sessions did not result in accumulation or accelerated metabolism of cephapirin. Ten infectious episodes in nine patients were treated in this manner with good clinical results and no toxicity.
In Vitro Activity of Cefaclor Against Aerobic and Anaerobic Bacteria
Authors: Bach Vinh T. , Khurana Mohini M. , Thadepalli Haragopal
Published: June 2012

Cefaclor (CCL), a new cephalosporin, was tested in vitro against 602 (271 anaerobic and 331 aerobic) clinical isolates in comparison with cephalothin, cefazolin, cephradine, and cefamandole. Sixteen micrograms of CCL per ml inhibited 68% of all aerobes tested and 80% of the 211 enteropathogenic organisms (
Escherichia coli, Salmonella
, and
Shigella
) isolated from cases of infantile diarrhoea. CCL inhibited 88% of gram-positive anaerobic cocci and 72% of
Bacteroides
other than
B. fragilis
at a concentration of 16 μg/ml.
B. fragilis
and
Clostridia
were resistant to CCL. Increased inoculum of
E. coli
from 10
5
to 10
9
increased the minimal inhibitory concentration of CCL and cefamandole by fourfold against 7 of the 64 strains tested. All seven were beta-lactamase negative. No antimicrobial synergism was noted between CCL and penicillin. The in vitro efficacy of CCL, an oral cephalosporin, against enteropathogenic
E. coli
, if proven safe, may be tested in vivo against such infections.
Diffusion Disk Susceptibility Testing with Cefaclor
Authors: Shadomy Smith , Carver Melinda
Published: June 2012

The reliability of the standardized 30-μg cephalothin disk and that of an experimental 30-μg cefaclor disk in predicting probable clinical susceptibility to cefaclor were compared. Quantitative determinations of cefaclor susceptibility were measured by the World Health Organization International Collaborative Study agar dilution procedure; diffusion disk tests were performed by the standardized U.S. Food and Drug Administration disk test. The cephalothin disk erred in predicting probable susceptibility in 52% of isolates of
Enterococcus
spp. resistant to 16 μg or less of cefaclor per ml; the cefaclor disk did not. The cephalothin disk erred in correctly predicting susceptibility in only 20% of cefaclor-susceptible isolates of
Enterobacter
spp.; the cefaclor disk correctly predicted susceptibility for 70%. These results indicate the need for further evaluation of a separate cefaclor disk for use in susceptibility testing with this new cephalosporin.
Reevaluation of the Mode of Action of Streptolydigin in
Escherichia coli:
Induction of Transcription Termination In Vivo
Authors: Meyenburg Kaspar Von , Nielsen Lissie Dahlgren , Johnsen Knud , Molin Søren , Svenningsen Bo , Miozzari Guiseppe
Published: June 2012

Growth of the permeable strain AS19 of
Escherichia coli
B is more sensitive to the antibiotic streptolydigin than is in vitro ribonucleic acid (RNA) synthesis. The in vivo chain elongation rates of
lacZ
messenger RNA and ribosomal RNA are not affected at 1.5 × 10
−6
M, a concentration that reduces the growth rate threefold. The synthesis of large proteins is inhibited preferentially, and a considerable fraction of the polypeptides synthesized is unstable. The synthesis of complete β-galactosidase is inhibited relative to the synthesis of short, unstable polypeptides, which include the first 60 to 70 amino acids of β-galactosidase. The expression of the following polycistronic transcription units is strongly biased against promoter-distal genes:
trp, deo, rpoBC
, and
rrn
. The extent of polarity is proportional to the distance transcribed and to the streptolydigin concentration. Streptolydigin appears to destabilize active transcription complexes irreversibly irrespective of the type of transcript (messenger RNA, ribosomal RNA) and of transcription intensity. We suggest that streptolydigin leads to premature termination of transcription, resulting in release of incomplete transcripts and, thus, a decrease in overall messenger RNA concentration, which becomes limiting for protein synthesis, i.e., for growth.
Secretion of Cell Wall Polymers into the Growth Medium of Lysis-Defective Pneumococci During Treatment with Penicillin and Other Inhibitors of Cell Wall Synthesis
Authors: Waks Susan , Tomasz Alexander
Published: June 2012

Autolysin-defective pneumococci secrete into the growth medium choline-containing macromolecules during treatment with any one of a large number of inhibitors of cell wall biosynthesis, including beta-lactams, beta-halogeno-
d
-alanines, cephalosporins, and
d
-cycloserine. Secretion is closely related to the dose response of the bacteria to the various drugs: (i) secretion can already be detected at the minimum inhibitory concentration; (ii) the rate and extent of secretion is dependent upon the drug concentration; and (iii) secretion commences within minutes after the addition of the antibiotics to the cultures. Reversal of the growth-inhibitory effect of benzylpenicillin (by penicillinase addition) is accompanied by a halt in secretion just at the time when the bacteria resume normal growth. Secretion of the choline-containing macromolecules seems to be a specific consequence of the inhibition of peptidoglycan biosynthesis, since inhibition of growth by drugs affecting protein, ribonucleic acid, or deoxyribonucleic acid synthesis does not cause secretion. The choline-containing macromolecules include both the pneumococcal lipid-containing teichoic acid (Forssman antigen) and wall teichoic acids made after the addition of antibiotics. The appearance of these macromolecules in the growth medium is not due to the hydrolytic activity of an autolysin, since penicillin-induced secretion could be demonstrated in autolysin-defective mutants, in pneumococci grown on ethanolamine-containing medium (such cells are known to have defective autolytic systems), and in wildtype pneumococci grown under conditions nonpermissive for lysis.
Treatment of a Murine Cytomegalovirus Infection with Exogenous Interferon, Polyinosinic-Polycytidylic Acid, and Polyinosinic-Polycytidylic Acid–Poly-
l
-Lysine Complex
Authors: Kern Earl R. , Olsen Gregg A. , Overall James C. , Glasgow Lowell A.
Published: June 2012

Treatment of a cytomegalovirus infection of mice with exogenous murine interferon did not alter final mortality or mean day of death. Pretreatment with two interferon inducers significantly reduced mortality, but treatment initiated after infection was not effective.
Aminoglycoside antibiotics moderately impair granulocyte function
Authors: Seklecki M M , Quintiliani R , Maderazo E G
Published: June 2012

By in vitro methods, five aminoglycoside antibiotics (amikacin, kanamycin, gentamicin, tobramycin, and netilmicin) were shown to produce modest changes in granulocyte adherence (increase) and migration (decrease) and no change in phagocytosis or nitroblue tetrazolium reduction.
Activity of Azlocillin and Mezlocillin Against Gram-Negative Organisms: Comparison with Other Penicillins
Authors: Wise R. , Gillett A. P. , Andrews J. M. , Bedford K. A.
Published: June 2012

The activities of azlocillin and mezlocillin were compared with those of carbenicillin, ticarcillin, and pirbenicillin against a wide range of gram-negative organisms. The two new drugs were considerably more active than carbenicillin against
Klebsiella
species and
Escherichia coli
. Carbenicillin was twice as active against
Proteus mirabilis
as mezlocillin and four times as active as azlocillin. Against
Pseudomonas aeruginosa
, azlocillin was eight times as active as carbenicillin. Azlocillin and mezlocillin were twice as active as carbenicillin against
Bacteroides fragilis
, and these drugs showed a high degree of activity against
Haemophilus influenzae
and
Neisseria gonorrhoeae
.
Use of a Heavy Inoculum in the In Vitro Evaluation of the Anti-Staphylococcal Activity of 19 Cephalosporins
Authors: Laverdiere Michel , Welter Diane , Sabath L. D.
Published: June 2012

The in vitro activity of 19 cephalosporins against 105 clinical isolates of
Staphylococcus aureus
and
S. epidermidis
was determined by using a heavy inoculum, i.e., 10
8
to 10
9
organisms per ml, to maximally challenge the antibiotics. The anti-staphylococcal activities of cephaloridine and 87/312 were consistently decreased by the use of a heavy inoculum when compared with the activity obtained with two less-concentrated inocula. The activity of most of the other compounds was also decreased with the use of a heavy inoculum, but this was observed only with selected isolates. Cephapirin, cephalothin, and cefazaflur were the most active drugs against the methicillin-susceptible isolates. Cephaloridine, cefamandole, cefazaflur, and 87/312 had substantial activity against methicillin-resistant staphylococci even with heavy inocula. With the exception of cefaclor against
S. aureus
, the orally absorbed cephalosporins were generally one-half to one-sixteenth as active as the parenterally administered cephalosporins. The median minimal inhibitory concentrations of five of the 12 parenteral cephalosporins were lower with the methicillin-susceptible
S. aureus
than with the methicillin-susceptible
S. epidermidis
strains.
Plasmid-Mediated Mechanisms of Resistance to Aminoglycoside-Aminocyclitol Antibiotics and to Chloramphenicol in Group D Streptococci
Authors: Courvalin Patrice M. , Shaw William V. , Jacob Alan E.
Published: June 2012

Genes conferring resistance to aminoglycoside-aminocyclitol antibiotics in three group D streptococcal strains,
Streptococcus faecalis
JH1 and JH6 and
S. faecium
JH7, and to chloramphenicol in JH6 are carried by plasmids that can transfer to other
S. faecalis
cells. The aminoglycoside resistance is mediated by constitutively synthesized phosphotransferase enzymes that have substrate profiles very similar to those of aminoglycoside phosphotransferases found in gram-negative bacteria. Phosphorylation probably occurs at the aminoglycoside 3′-hydroxyl group. Plasmid-borne streptomycin resistance is due to production of the enzyme streptomycin adenylyltransferase, which, as in staphylococci and in contrast to that detected in gram-negative bacteria, is less effective against spectinomycin as substrate. Resistance to chloramphenicol is by enzymatic acetylation. The chloramphenicol acetyltransferase is inducible and bears a close resemblance to the type D chloramphenicol acetyltransferase variant from staphylococci.
Trypanocidal Activity of Antitumor Antibiotics and Other Metabolic Inhibitors
Authors: Williamson J. , Scott-Finnigan T. J.
Published: June 2012

A microtest has been devised for the rapid preliminary assay in vitro of the effect of over 100 drugs and inhibitors on African trypanosomes (
Trypanosoma brucei
and
T. rhodesiense
). Parasite motility and infectivity for mice are indexes, respectively, of respiration and glycolysis and of cell division; trypanocidal titers based on these indexes can show primary metabolic areas of drug attack. Various specific inhibitors have also been tested to detect metabolic sites which might be therapeutically vulnerable. RNA synthesis inhibitors are highly active (adenine nucleosides, daunorubicin, doxorubicin, chromomycin, actinomycin D, mitomycin C); the activity of the nucleoside cordycepin was increased in vitro and in vivo by an adenosine deaminase inhibitor. In view of the polyanionic nature of the trypanocide suramin, a series of polyanions was tested; several showed activity but only poly-
d
-glutamic acid was active in vivo. Among various miscellaneous inhibitors, quercetin, disulfiram, and the Ca-complexing agents arsenazo I and III showed marked activity, the latter exclusively on the arsenical-resistant
T. brucei
. The implications of these results for combination chemotherapy and depot prophylaxis (with polyanions) are indicated.
Synergy of Azlocillin and Mezlocillin Combined With Aminoglycoside Antibiotics and Cephalosporins
Authors: Neu Harold C. , Fu Kwung P.
Published: June 2012

Synergistic activity between both azlocillin and mezlocillin and aminoglycosides or cefazolin could be demonstrated by checkerboard dilution, isobologram, and killing curve techniques. Azlocillin and mezlocillin combined with gentamicin, netilmicin, or amikacin were synergistic against
Escherichia coli, Klebsiella, Citrobacter, Enterobacter, Serratia
, and indole-positive
Proteus
. Synergy was observed with isolates that were susceptible or resistant to azlocillin or mezlocillin. Synergy was seen most often when azlocillin or mezlocillin were combined with amikacin, gentamicin, or netilmicin against
Pseudomonas aeruginosa
. The combination of mezlocillin and an aminoglycoside produced synergy more often than did carbenicillin plus an aminoglycoside. No antagonism was seen when aminoglycoside antibiotics were combined with azlocillin or mezlocillin. Cefazolin was synergistic against
Pseudomonas, Providencia, P. mirabilis
, indole-positive
Proteus, Citrobacter, Klebsiella
, and
Escherichia coli
, when combined with azlocillin or mezlocillin. However, the combination of either agent with cefazolin was antagonistic when tested against selected indole-positive
Proteus
and
Enterobacter
isolates.
In Vitro Susceptibility Studies with Netilmicin: Comparison of a 10-μg Netilmicin Disk with a Standardized 10-μg Gentamicin Disk
Authors: Habwe Violet , Shadomy Smith
Published: June 2012

Netilmicin is a new, semisynthetic aminoglycoside antibiotic active against some gentamicin-resistant gram-negative bacteria. In this study we compared a 10-μg netilmicin disk with the standardized 10-μg gentamicin disk in terms of their abilities to predict probable clinical susceptibility to netilmicin. The agar dilution procedure of the International Collaborative Study of the World Health Organization and the U.S. Food and Drug Administration standardized disk test procedure were used. The gentamicin disk failed to predict the clinical susceptibility to netilmicin of 26 of 118 isolates previously shown by the agar dilution technique to to be netilmicin susceptible. The netilmicin disk correctly predicted probable susceptibility of all 26 isolates, including 20 shown by the agar dilution procedure to be resistant to gentamicin. These studies demonstrate the need for a separate netilmicin disk for use in agar diffusion disk susceptibility tests.
In Vitro Activity and Beta-Lactamase Stability of BL-S786 Compared with Those of Other Cephalosporins
Authors: Aswapokee Nalinee , Aswapokee Prasit , Fu Kwung P. , Neu Harold C.
Published: June 2012

In vitro activity of BL-S786, a new parenterally semisynthetic cephalosporin, was investigated against 570 bacterial isolates. BL-S786 inhibited most
Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis
, and
Salmonella
. It inhibited some
Enterobacter
and indole-positive
Proteus
, but it was less active against these later species than was cefamandole, cefuroxime, or cefoxitin. It was not active against
Serratia marcescens, Pseudomonas aeruginosa
, or
Bacteroides fragilis
. BL-S786 was the least active new cephalosporin tested against staphylococci and was less active than cephalothin against streptococcal species. The activity of BL-S786 was not altered by the type of assay medium nor by 50% serum. The size of the test inoculum altered the minimal inhibitory and bactericidal concentrations for inhibition of some organisms, particularly those with Richmond type I β-lactamases. BL-S786 was not hydrolyzed by the R-factor-mediated, Richmond type III β-lactamase, but it was hydrolyzed by type I β-lactamases.
Mode of Action of a Structurally Novel Beta-Lactam
Authors: Presslitz Joseph E.
Published: June 2012

CP-35,587 {6-[
d
-2-amino-2-(
p
-hydroxyphenyl)acetamido]-2,2-dimethyl-3- (5-tetrazolyl)-penam} is a member of a new family of β-lactam antibacterial agents. Because the biospectrum of CP-35,587 has features similar to both penicillins and cephalosporins, experiments were carried out to explore its mode of action. CP-35,587 did not inhibit peptidoglycan transpeptidase from
Escherichia coli
, but it did inhibit
dd
-carboxypeptidase. Similar results were obtained with cephalexin. When these antibiotics were compared for effects on growth and morphology of
E. coli
, it was observed that filaments formed after exposure to either antibacterial agent for 30 to 60 min. The filaments enlarged, and fragmentation occurred until very few viable cells remained after exposure to CP-35,587. After 180 min in the presence of cephalexin, the cells began to divide, and the filaments formed cross-walls reaching control values in 24 h. CP-35,587 and cephalexin had similar effects on the morphology of the
Klebsiella
cell: the cells became enlarged within 30 min; with increasing exposure, the filaments became longer, with evidence of cytoplasmic emptying and ghost cell formation. These ghostlike tubules eventually broke apart, leaving fragments. These data indicate differences in the mode of action of CP-35,587 from those of most other β-lactam antibiotics.
Molecular Studies and Possible Relatedness Between R Plasmids from Groups B and D Streptococci
Authors: El-Solh Névine , Bouanchaud D. H. , Horodniceanu Théa , Roussel Agnès , Chabbert Y. A.
Published: June 2012

Resistance plasmids isolated from
Streptococcus agalactiae
(group B) and
S. faecalis
(group D) have been compared in regard to resistance markers, molecular weight, and DNA-DNA homology. Three of them (pIP501, pIP612, and pIP613) have been found to confer identical (or very similar) resistance patterns (erythromycin, lincomycin, and streptogramin B, respectively) and to have similar molecular weights (19.8 × 10
6
, 22.7 × 10
6
, and 17.6 × 10
6
, respectively) and a high level of DNA-DNA homology in hybridization experiments (90 to 100%). These results are compatible with the view that these plasmids may derive from one common ancestor, and/or that they can be transferred between unrelated
Streptococcus
strains belonging to the same or different groups.
Pharmacokinetics of Netilmicin in the Presence of Normal or Impaired Renal Function
Authors: Humbert G. , Leroy A. , Fillastre J. P. , Oksenhendler G.
Published: June 2012

A pharmacokinetic study of netilmicin was conducted in 12 healthy subjects and 24 subjects with chronic renal failure. After intramuscular administrations of 2 and 3 mg of netilmicin per kg in normal subjects, the mean peak serum concentrations were 5.46 and 8.83 μg/ml, respectively. After intravenous infusions of identical doses, the mean maximum serum levels, occurring at the end of the infusion, were 11.79 and 15.75 μg/ml, respectively. The pharmacokinetic data were very similar via the two routes of administration and for the two doses. The elimination half-life was 2.20 h, and 80 to 90% of the injected dose was recovered in urine during the first 24 h. After intramuscular administration of 2 mg/kg in subjects with chronic renal impairment, the elimination half-life increased to 29.48 h, and urinary elimination was inversely related to the degree of impairment. A study was conducted throughout hemodialysis sessions: serum concentrations decreased by 63.3%. The linear relationships between the elimination rate constant and creatinine clearance and the elimination half-life and serum creatinine allowed us to establish dosage schedules according to the degree of renal failure.
Fluorescent Assay for Estimating the Binding of Erythromycin Derivatives to Ribosomes
Authors: Brandt-Rauf Paul , Vince Robert , LeMahieu Ronald , Pestka Sidney
Published: June 2012

A fluorescent erythromycin derivative was used to determine the binding of erythromycin derivatives to ribosomes. The assay is rapid, sensitive, and convenient. Because measurements are made in solution, they represent equilibrium conditions, unlike filter binding assays which perturb the equilibrium. Results correlate well with measurements made by other techniques.
Pharmacokinetics of Gentamicin Administered Intratracheally to Rats
Authors: Trnovec Tomáš , Navarová Jana , Kettner Milan , Gregušková Mária , Bezek Štefan , Gajdošík Andrej , Kyselova Alena
Published: June 2012

The pharmacokinetics of intratracheally instilled and intravenously injected gentamicin were compared in the rat and analyzed by a one-compartment open model. The maximum concentration of gentamicin in plasma occurred within 10 min after intratracheal instillation. Considerable amounts of gentamicin were absorbed from lungs after intratracheal instillation, as shown by its concentrations in plasma and elimination in urine. The data suggest that the absorption of gentamicin from the pulmonary system would be sufficient to maintain therapeutic levels of this agent in plasma.
Improved Radioenzymatic Assay for Spectinomycin
Authors: Cannon Janne G. , Moran Charles P. , Bott Kenneth F.
Published: June 2012

The sensitivity and reproducibility of the radioenzymatic adenylylating assay for spectinomycin were improved by modifications of the assay procedure and by partial purification of the enzyme. The presence of
Bacillus subtilis
ribosomes or S-150 fraction in the enzymatic reaction mixture interfered with the ability to measure spectinomycin by this method.
In Vitro Studies with UK-18,892, a New Aminoglycoside Antibiotic
Authors: Jevons S. , Cheeseman H. E. , Brammer K. W.
Published: June 2012

The antibacterial activity of UK-18,892, a new semisynthetic aminoglycoside, was examined against aminoglycoside-susceptible and aminoglycoside-resistant clinical isolates of gram-negative bacilli and
Staphylococcus aureus
. UK-18,892 had a similar degree of activity to those of amikacin and kanamycin A against aminoglycoside-susceptible bacteria but was less potent than gentamicin against all isolates except
Providencia
spp. UK-18,892 was highly active against aminoglycoside-resistant bacteria, inhibiting 93% of the 268 isolates examined at 12.5 μg/ml. Amikacin was similarly active, whereas gentamicin inhibited only 14% of these isolates at 12.5 μg/ml.
Effects of Hypoxemia upon Aminoglycoside Serum Pharmacokinetics in Animals
Authors: Mirhij Najwa J. , Roberts Robert J. , Myers Martin G.
Published: June 2012

Hypoxemia causes significant alterations in aminoglycoside serum pharmacokinetics in adult rats and newborn rabbits. The aminoglycoside serum clearances were diminished in hypoxemic animals. Comparisons of intravenous and intramuscular administration imply a delay in uptake of drug from intramuscular injection sites under hypoxemic conditions.
Amphotericin B and 5-Fluorocytosine: In Vitro Effects on Lymphocyte Function
Authors: Roselle Gary A. , Kauffman Carol A.
Published: June 2012

The effects of amphotericin B, 5-fluorocytosine, and the combination of both drugs on lymphocyte function in vitro were investigated. Amphotericin B, alone or in combination with 5-fluorocytosine, significantly suppressed both spontaneous lymphocyte transformation and the response of lymphocytes to stimulation with streptokinase-streptodornase. 5-Fluorocytosine had no effect on spontaneous or antigen-induced transformation. Lymphocyte responses to the mitogens phytohemagglutinin and concanavalin A were not changed by exposure to amphotericin B, 5-fluorocytosine, or the combination of both drugs. T-lymphocyte receptors for sheep erythrocytes and B-lymphocyte surface immunoglobulin and receptors for complement were not changed by treatment with amphotericin B or 5-fluorocytosine.
Pharmacokinetics of Netilmicin in Patients with Renal Impairment and in Patients on Dialysis
Authors: Luft Friedrich C. , Brannon David R. , Stropes Linda L. , Costello Robert J. , Sloan Rebecca S. , Maxwell Douglas R.
Published: June 2012

The pharmacokinetics of netilmicin were examined in 25 adult subjects, 7 normal subjects, and 18 patients with renal impairment. Five were dialysis patients who were studied on and off dialysis. Netilmicin, 2 mg/kg, was infused intravenously over 1 h. The peak serum concentration ranged from 9 to 11 μg/ml. The mean biological half-life of netilmicin for subjects with a creatinine clearance (Ccr) > 70 ml/min was 2.7 h, for those with Ccr > 25 < 70 ml/min it was 10 h, for those with Ccr > 4 < 25 ml/min it was 32 h, and for those who were anephric it was 42 h. Ccr was correlated positively with the elimination constant and the drug's serum clearance. It was negatively correlated with the drug's volume of distribution. The dialyzer clearance of netilmicin was positively correlated with plasma flow rate and was similar to values previously reported for gentamicin. Netilmicin behaves in a fashion similar to other aminoglycosides. Therapeutic guidelines are suggested.
Effects of Radiopharmaceuticals on Radioenzymatic Assays of Aminoglycoside Antibiotics: Interference by Gallium-67 and Its Elimination
Authors: Bhattacharya Ishan , Seligsohn Robert , Lerner Stephen A.
Published: June 2012

Radionuclides currently used in clinical medicine were evaluated for their possible interference with radioenzymatic assays of aminoglycoside antibiotics. Of the radiopharmaceuticals tested, only
67
Ga citrate interfered with the radioenzymatic assay of gentamicin. Radioenzymatic assay of serum samples obtained from patients receiving
67
Ga yielded gentamicin concentrations falsely elevated by more than 1 μg/ml for approximately 1 week after
67
Ga administration. A procedure was developed to eliminate
67
Ga interference with radioenzymatic assays of aminoglycoside antibiotics. After
67
Ga citrate was spotted onto phosphocellulose filter disks, the filters were immersed in 7.2 N HCl, and radioactivity was removed by successive extractions of the acid phase with diisopropyl ether. After three extractions, less than 0.1% of the original radioactivity remained. Similar extraction of disks containing
14
C-adenylylated gentamicin or tobramycin or
14
C-acetylated amikacin had no effect on
14
C radioactivity. The concentrations of aminoglycosides in serum standards supplemented with
67
Ga citrate were determined accurately by radioenzymatic assays followed by extraction with diisopropyl ether. Concentrations of gentamicin in six serum samples from patients injected with
67
Ga during gentamicin therapy, as determined by radioenzymatic assay and extraction, were within 9% of the results obtained by reassay of the same samples after the decay of
67
Ga.
Inosiplex for Localized Herpes Zoster in Childhood Cancer Patients: Preliminary Controlled Study
Authors: Feldman S. , Hayes F. A. , Chaudhary S. , Ossi M.
Published: June 2012

By multiple criteria, inosiplex—a reputed stimulator of virus-sensitized lymphocytes—had no demonstrable therapeutic effects in a preliminary controlled study of patients with localized herpes zoster and cancer. Lymphocytes from the six drug-treated patients were no more responsive to varicella-zoster antigen and phytohemagglutinin than were lymphocytes from seven patients who received a placebo.
Proposed Ticarcillin Disk Control Values for
Escherichia coli
and
Pseudomonas aeruginosa
: Multicenter Cooperative Study
Authors: Prior Richard B. , Fass Robert J.
Published: June 2012

In a multicenter cooperative controlled study, individual test, accuracy, and precision control values were determined for 75-μg ticarcillin disks with
Escherichia coli
ATCC 25922 and
Pseudomonas aeruginosa
ATCC 27853.
Quantitation of Imidazoles by Agar-Disk Diffusion
Authors: Grendahl Jan G. , Sung James P.
Published: June 2012

A simple, reliable, and inexpensive assay for quantitation of the imidazole drugs miconazole, RV 40,500, and RV 41,400 was tested. The assay, similar to a Kirby-Bauer test, was sensitive to less than or equal to 0.2 μg of drug per ml and linear from less than or equal to 0.2 to 10.0 μg/ml. Concentration of inoculum and agar depth in test plates was not as critical as the type of medium, amount of inoculum, or type of drug used.