bluuebunny/crossref_metadata_2025 huggingface dataset:
Mode of Action of Penicillins In Vivo and In Vitro in
Bacillus megaterium
Authors: Oka Tetsuo
Published: June 2012

A new system in which the in vivo and in vitro formation of cross-links in the peptidoglycan of
Bacillus megaterium
can be compared directly has been developed. The method for the determination of the in vivo cross-linking consists of lysozyme digestion of acetylated [
14
C]diaminopimelic acid-labeled cells and Bio-Gel P-6 gel filtration of the digest. The elution profile indicates the cell wall synthesized in vivo consists of highly cross-linked fractions (44%), bisdisaccharide peptide(s) (38%), and disaccharide peptide(s) (18%). The in vitro system showed a high synthetic activity of cross-linked peptidoglycan. The synthesis was inhibited completely by 83.3 μg of ristocetin or vancomycin per ml or 10
−4
M
p
-chloromercuribenzoate and inhibited only partially by penicillins. The polymerization was stimulated by high concentrations of sucrose, glycerol, amino acids, or dimethyl sulfoxide. The formation of cross-links was inhibited 50% at 0.3 μg of dicloxacillin per ml and 90% at 0.5 μg or more. It was also stimulated by high concentrations of sucrose, glycerol, or dimethyl sulfoxide. Effective concentrations of dicloxacillin on the growth, viability, and morphology of
B. megaterium
were determined. Sharp inhibition of cross-linking occurred in vivo and in vitro at these effective concentrations, whereas the incorporation of [
14
C]-diaminopimelate into bacterial cells was not affected at all. Cell-bound dicloxacillin reduced severely the degree of cross-linking in the cell wall synthesized after transfer to a dicloxacillin-free medium. Cell wall synthesized in the presence of dicloxacillin showed a higher rate of turnover than did the normal cell wall. Moreover, disaccharide peptide(s) was degraded faster than was bisdisaccharide peptide(s) in dicloxacillin-treated cells. From these observations, the primary target of penicillin action in
B. megaterium
is discussed in relation to the inhibition of cross-linking, penicillin-binding components, and cell lysis.
Synergistic Activity of Carbenicillin and Gentamicin in Experimental
Pseudomonas
Bacteremia in Neutropenic Rats
Authors: Scott Rita E. , Robson Hugh G.
Published: June 2012

Rats made neutropenic with cyclophosphamide were infected intraperitoneally with
Pseudomonas aeruginosa
. The challenge organism was killed synergistically in vitro by the combination of gentamicin and carbenicillin. Untreated neutropenic rats infected with 3 × 10
6
Pseudomonas
died between days 2 and 7, and the overall mortality was 70%. Groups of infected neutropenic rats were treated intramuscularly with 1.5 or 6 mg of gentamicin per kg per dose, 100 or 400 mg of carbenicillin per kg per dose, or 1.5 mg of gentamicin and 100 mg of carbenicillin per kg per dose. Treatment was begun at 2 h postinfection and was continued every 8 h for about 72 h. Cultures of blood and peritoneal washings were performed in control and treated rats at 1, 4, 24, 48, and 72 h postinfection. Gentamicin at either dose level was ineffective in preventing death, but mortality was significantly reduced by high-dose carbenicillin and low-dose combination therapy. In addition, the latter regimens sterilized the peritoneal fluid and blood. Carbenicillin and gentamicin showed in vivo synergy in the treatment of neutropenic
Pseudomonas
-infected rats.
Susceptibility of Anaerobic Bacteria to 23 Antimicrobial Agents
Authors: Sutter Vera L. , Finegold Sydney M.
Published: June 2012

The antimicrobial susceptibility of 492 anaerobic bacteria, the majority of which were recent clinical isolates, was determined by the agar dilution technique. Penicillin G was active against most of the strains tested at 32 U or less/ml, but only 72% of
Bacteroides fragilis
strains were susceptible at this level and 9% required 256 U or more/ml. Ampicillin was effective against most of the strains except
B. fragilis
at 16 μg or less/ml. Amoxicillin was active against only 31% of
B. fragilis
, 76% of other
Bacteroides
species, and 67% of
Fusobacterium
species at 8 μg/ml. Two new penicillins, mezlocillin and azlocillin, were similar to ampicillin in their activity. Carbenicillin and ticarcillin inhibited all but a few strains at 128 μg or less/ml. BLP 1654 was somewhat more active than penicillin G against
B. fragilis
but had similar activity against other anaerobes. Cephalothin was inactive against
B. fragilis
, and only 65% of other
Bacteroides
species were inhibited by 32 μg or less/ml. It was effective against all other anaerobes at that level. Cefamandole showed somewhat greater activity than cephalothin against
B. fragilis
but generally less activity against gram-positive organisms. Cefazaflur (SKF 59962) was comparable to cephalothin against
B. fragilis
. Cefoxitin was distinctly more active than cephalothin against
B. fragilis
. These latter two agents were less active than cephalothin against the gram-positive anaerobes. Chloramphenicol remains active against anaerobic bacteria at 16 μg or less/ml, with rare exceptions. Thiamphenicol was similar to chloramphenicol in its activity. Clindamycin was very active against most of the anaerobes at 8 μg or less/ml. Erythromycin and josamycin were also tested, with josamycin showing greater activity against
B. fragilis
than either erythromycin or clindamycin. A new oligosaccharide, everninomicin B, was less active than clindamycin against
B. fragilis
but more active against clostridia and some of the other strains tested. Most of the groups of bacteria tested demonstrated a trend toward resistance to tetracycline. Doxycycline and minocycline were somewhat more active than was tetracycline. Metronidazole was active against the majority of the anaerobes tested; resistance ws demonstrated by some of the gram-positive cocci and gram-positive, non-sporeforming bacilli.
Comparative Nephrotoxicities of Netilmicin and Gentamicin in Rats
Authors: Luft Friedrich C. , Yum Moo Nahm , Kleit Stuart A.
Published: June 2012

The relative nephrotoxicities of netilmicin (Sch 20569) and gentamicin were compared in rats at doses of 30, 60, 90, and 120 mg/kg per day for 15 days. Both drugs caused proteinuria and a decrease in urine osmolality; however, netilmicin produced significantly less changes at all doses than gentamicin. Whereas gentamicin resulted in a decline in creatinine clearance at all doses, netilmicin failed to cause a decline in creatinine clearance. Renal-cortical concentrations of antibiotic at sacrifice were similar in animals receiving either drug. Light-microscopic changes were less severe with netilmicin than gentamicin. Cytosegresomes with myeloid bodies were identified electron microscopically in the kidneys of animals receiving either netilmicin or gentamicin at all doses. Electron-microscopic manifestations were similar. The data indicate that in the rat, netilmicin is distinctly less nephrotoxic than gentamicin.
Preparation of Isolated Intestinal Villi Useful for Studying Hydrolysis Rates of Penicillin and Cephalosporin Esters
Authors: Wright Walter E. , Line Verle D.
Published: June 2012

A method for the preparation of freeze-dried intestinal villi from hamsters and mice is described. The villi, consisting largely of epithelial cells rich in esterase activity, are useful for hydrolysis studies of penicillin and cephalosporin esters.
Bacteriocin Production by Group A Streptococcal L-Forms
Authors: Hryniewicz Waleria , Tagg John R.
Published: June 2012

L-forms induced from a bacteriocin-producing strain of group A streptococcus retained both the ability to produce the streptococcin and producer strain immunity to the homologous bacteriocin. L-forms of a spontaneously cured (bacteriocin negative) derivative of this same strain failed to produce streptococcin but were sensitive to its action.
Medium for Use in Antibiotic Susceptibility Testing of Anaerobic Bacteria
Authors: Wilkins Tracy D. , Chalgren Sarah
Published: June 2012

A medium is described which was designed for use in testing the minimal inhibitory concentration of antibiotics for anaerobic bacteria by agar dilution. It contains: Trypticase (1%), Gelysate (1%), yeast extract (0.5%), glucose (0.1%), pyruvate (0.1%), arginine (0.1%), NaCl (0.5%), hemin (5 μg/ml), vitamin K
1
(0.5 μg/ml), agar (1.5%). The medium does not require the addition of blood to support growth of most clinical isolates of anaerobic bacteria.
Bactericidal Effects of Combinations of Ampicillin with Anti-R-Plasmid Compounds on
Salmonella typhimurium
R1
+
Authors: Hahn Fred E. , Ciak Jennie
Published: June 2012

Salmonella typhimurium
R1
+
, resistant to 2,500 μg of ampicillin per ml, was rapidly killed by combinations of 60 μg of ampicillin per ml with quinacrine (4 × 10
−4
M), ethidium bromide (10
−4
M), tilorone (10
−4
M), or Nitroakridin 3582 (5 × 10
−6
M).
Bioassay Method for Polyene Antibiotics Based on the Measurement of Rubidium Efflux from Rubidium-Loaded Yeast Cells
Authors: Cosgrove R. F. , Fairbrother J. E.
Published: June 2012

A bioassay method for the polyene antibiotics nystatin and amphotericin B is proposed based on the measurement of the efflux of rubidium ions from a rubidium-loaded yeast culture challenged with the antibiotics. For this purpose a major proportion of the intracellular K
+
ions in a
Saccharomyces cerevisiae
culture has been substituted by Rb
+
ions. The rubidium leakage is measured by atomic absorption spectrophotometry, and a straight-line, dose-response correlation has been obtained for both antibiotics.
Synthesis of Vaccinia Viral Antigens in HeLa Cells in the Presence of Isatin Beta-Thiosemicarbazone
Authors: Katz Ehud , Felix Haya
Published: June 2012

Vaccinia virus antigens, in HeLa cells treated with the antipox virus drug isatin β-thiosemicarbazone (IBT), were analyzed by immunoprecipitation, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The total radioactivity in the immunoprecipitate was decreased to almost 50% in the presence of the drug as compared to its absence. An inhibition also occurred with an IBT-dependent mutant (IBT
D
) when growing in the absence of IBT. However, similar levels of radioactivity were observed in the immunoprecipitates from an IBT-resistant mutant (IBT
R
) grown in either the absence or presence of the drug. When the antigens within the immunoprecipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, it was shown that the inhibition observed in the wild-type-infected cells in the presence of IBT and in the IBT
D
-infected cells in the absence of the drug, was quantitative, affecting the amounts of the different polypeptides more or less equally.
Antimicrobial Prophylaxis for Catheter-Associated Bacteriuria
Authors: Britt Michael R. , Garibaldi Richard A. , Miller William A. , Hebertson Richard M. , Burke John P.
Published: June 2012

We evaluated short-term systemic antimicrobial prophylaxis for catheter-associated bacteriuria in women undergoing elective gynecological operations in a prospective, controlled, double-masked study. Nine of 100 placebo-treated patients acquired bacteriuria during catheterization compared with 3 of 96 of the drug-treated group. However, at the time of hospital discharge, clean-voided urine specimens were positive as frequently in the drug-treated group (8 of 82 patients cultured) as in the placebo group (8 of 75 patients cultured). No difference in febrile morbidity due to bacteriuria was noted between the prophylaxis and placebo groups. The incidence of catheter-associated bacteriuria may be reduced by antimicrobial prophylaxis. However, because the protective effect is transient and is associated with the selection of resistant organisms, prophylaxis is not indicated for patients at low risk for acquired bacteriuria and in whom the sequelae of catheter-associated infections are infrequent.
Hemagglutination Inhibition Assay for Gentamicin
Authors: Mahon W. A. , Feldman Rhoda I. , Scherr George H.
Published: June 2012

A rapid and simple hemagglutination inhibition test for measuring gentamicin concentrations in serum has been developed. Correlation coefficients for this assay with the radioimmunoassay and microbiological assay were
r
= 710 and
r
= 0.864, respectively. Measurements of gentamicin levels in serum by the three methods showed no statistically significant differences. The hemagglutination inhibition assay is fast, reliable, and relatively inexpensive, and should prove valuable for laboratory use.
Comparative Trial of Carbenicillin and Ampicillin Therapy for Purulent Meningitis
Authors: Overturf G. D. , Steinberg E. A. , Underman A. E. , Wilkins J. , Leedom J. M. , Mathies A. W. , Wehrle P. F.
Published: June 2012

A randomized therapeutic trial of carbenicillin (CB) or ampicillin (AMP) in purulent meningitis was performed in 86 pediatric and adult patients (41
Haemophilus influenzae
, 22
Streptococcus pneumoniae
, 13
Neisseria meningitidis
, and 10 of unknown etiology). All isolates, incuding
H. influenzae
, were susceptible to CB and AMP. Median cerebrospinal fluid (CSF) antibiotic concentrations were 0.85 and 1.60 μg/ml for CB and AMP, respectively, during administration of daily doses of 400 mg/kg and 0.65 and 0.45 μg/ml, respectively, on daily doses of 200 mg/kg. Higher CSF concentrations, up to a median concentration of 4.5 μg/ml, were observed in patients with CSF protein concentrations ≥75 mg/100 ml. Clinical responses were equivalent on either antibiotic regimen. Among AMP patients (45), 8 had significant residua and 3 died; among CB patients (41), 5 had residua and none died. However, 38% of
H. influenzae
patients treated with CB had positive CSF cultures on day 1 follow-up lumbar punctures, compared with only 5.8% of AMP patients with
H. influenzae
. The significance of a delay of CSF sterilization among CB-treated patients is unknown, since there was no correlation between persistence of hemophilus organisms and the frequency of adverse outcome. AMP and CB are equivalent for the treatment of bacterial meningitis due to susceptible organisms.
Pirbenicillin: Comparison with Carbenicillin and BL-P1654, Alone and with Gentamicin, Against
Pseudomonas aeruginosa
Authors: Lopez Carlos E. , Standiford Harold C. , Tatem Beverly A. , Calia Frank M. , Schimpff Stephen C. , Snyder Merrill J. , Hornick Richard B.
Published: June 2012

Minimum inhibitory concentrations (MIC) of pirbenicillin against 135 clinical isolates of
Pseudomonas aeruginosa
were one-fourth of those required for carbenicillin but two times higher than those for BL-P1654. Increasing the inoculum size produced an adverse effect on the bactericidal activity for all three antibiotics. This was more apparent for pirbenicillin than for carbenicillin, but less than the effect on BL-P1654. When concentrations of antibiotics likely to be achieved clinically were used, gentamicin increased the inhibitory and bactericidal effects of all three semisynthetic penicillins for the majority of isolates. Strains highly resistant to the aminoglycoside antibiotic, however, were inhibited no more by the penicillin-gentamicin combinations than by the most effective of the antibiotics alone.
Bioavailability of Tetracycline and Doxycycline in Fasted and Nonfasted Subjects
Authors: Welling Peter G. , Koch Patricia A. , Lau Curtis C. , Craig William A.
Published: June 2012

The influence of various test meals and fluid volumes on the relative bioavailability of commercial formulations of doxycycline hyclate and tetracycline hydrochloride was studied in healthy human volunteers. Serum levels of tetracycline were uniformly reduced by approximately 50% by all test meals, whereas serum levels of doxycycline were reduced by 20%. The reduction of tetracycline serum levels will likely be of clinical significance. The bioavailability of each drug was almost identical from an oral solution and from capsules in fasted subjects. The rate of doxycycline absorption was reduced when capsules were administered with a small volume of water, but the overall efficiency of absorption of both drugs was essentially independent of co-administered fluid volume. The use of 8-h serum data provides a reliable estimate of drug bioavailability for tetracycline and, to a lesser extent, for doxycycline.
Comparative Growth Rates of Selected Anaerobic Species in Four Commonly Used Broth Media
Authors: Sottile William , Zabransky R. J.
Published: June 2012

Generations times (

g
t

) of selected anaerobic species were compared in four culture media commonly used for anaerobic bacteria to evaluate these media for growing inocula for anaerobic antibiotic susceptibility determinations. Twenty-two clinical isolates of
Bacteroides fragilis, Fusobacterium
spp.,
Clostridium perfringens
, and
Clostridium
spp. were tested in Schaedler broth, supplemented Lombard-Dowell broth, supplemented thioglycolate broth, and supplemented peptone-yeast extract-glucose broth. Growth curves were performed in an anaerobic chamber; changes in cell density were followed by viable count procedures and, in some cases, turbidometric procedures. The clostridia did not appear to have significantly different

g
t

values in different media. The

g
t

values for the five clostridial species tested ranged from 18 to 45 min. The fusobacteria also showed no apparent differences in

g
t

values in the four media; values ranged from 51 to 60 min. The two subspecies of
B. fragilis
tested showed no significant differences in

g
t

values when compared with each other in the same media. The combined data, however, indicated that the growth rate in Schaedler broth was faster than in the other media (average

g
t

, 45.1 min), whereas the growth rate in peptone-yeast extract-glucose was slower (average

g
t

, 58.2 min). The growth rates in supplemented thioglycolate and supplemented Lombard-Dowell broth (average

g
t

, 53.6 min and average

g
t

, 51.0 min, respectively) were not significantly different.
Mobilization of Morganocin 174 Plasmid and Kinetics of Morganocin Production in
Proteus
and
Escherichia coli
Hosts
Authors: Williams J. A.
Published: June 2012

Morganocin 174 is coded by a plasmid, Mor174. The plasmid is not self-transmissible but may be mobilized by resistance factor R772. Morganocin synthesis in all
Proteus
and
Providencia
strains carrying Mor174 was characterized by a longer lag period after induction and higher titers than in
Escherichia coli
B(Mor174). The low titers obtained in
E. coli
B(Mor174) are due to a heatstable inhibitor produced by this strain. Synthesis of morganocin is not constitutive and may be induced by ultraviolet irradiation or mitomycin C. Morganocin production is not influenced by the growth medium of the organism.
Antimicrobial Susceptibilities of
Yersinia enterocolitica
Biotype 4, Serotype O:3
Authors: Hammerberg S. , Sorger S. , Marks M. I.
Published: June 2012

Agar dilution antimicrobial susceptibility tests were carried out against recent clinical isolates of
Yersinia enterocolitica
biotype 4, serotype O:3. Aminoglycosides and co-trimoxazole were the most active drugs. All isolates were resistant to ampicillin, carbenicillin, cloxacillin, and erythromycin.
R Plasmids from Asian Strains of
Vibrio cholerae
Authors: Hedges R. W. , Vialard J. L. , Pearson N. J. , O'Grady F.
Published: June 2012

Five R plasmids transferred from Asian strains of
Vibrio cholerae
all proved to be members of compatibility group C. A non-self-transmissible plasmid, stable in
V. cholerae
, was mobilized for transfer to
Escherichia coli
K-12 and found to be unstably inherited in that host. Plasmids of group C and P transferred to a wild
V. cholerae
strain were stably inherited.
Pseudomonas aeruginosa
Strain Isolated in France That Carries a Plasmid Determining Carbenicillin Resistance
Authors: Michel-Briand Y. , Stanisich Vilma A. , Jouvenot M.
Published: June 2012

A plasmid, R56Be, derived from a clinical strain of
Pseudomonas aeruginosa
isolated in France in 1973 has been studied. This plasmid confers resistance only to carbenicillin, and although freely transferable between unrelated strains of
P. aeruginosa
, its transfer from
P. aeruginosa
to
Escherichia coli
K-12 was undetectable. R56Be could not be isolated as covalently closed circular deoxyribonucleic acid, but the plasmid could be transduced intact by phage F116L. This suggests that its molecular weight does not exceed that of the phage genome (ca. 40 × 10
6
). In terms of its interaction with male and female sex-specific phages, its exclusion characteristics, and the main properties of β-lactamase determined by them, R56Be is similar to the previously characterized plasmid RP1-1.
Levels of Carbenicillin, Ticarcillin, Cephalothin, Cefazolin, Cefamandole, Gentamicin, Tobramycin, and Amikacin in Human Serum and Interstitial Fluid
Authors: Tan James S. , Salstrom Sara Jane
Published: June 2012

The ability of eight antibiotics (carbenicillin, ticarcillin, cefamandole, cephalothin, cefazolin, gentamicin, tobramycin, and amikacin) to enter human interstitial fluid was evaluated by the skin window technique. All of the antibiotics tested, except cefazolin, which has the highest percentage of protein binding, diffused into the interstitial fluid quite well. This study confirms our previous observation on the effect of high-percentage protein binding on diffusion of a drug into the minimally inflamed extravascular space.
Permeability Barrier to Rifampin in Mycobacteria
Authors: Hui J. , Gordon N. , Kajioka R.
Published: June 2012

A strain of
Mycobacterium intracellulare
that exhibited natural resistance to rifampin was isolated. The ribonucleic acid polymerase was found to be susceptible to rifampin. Studies with Tween 80 suggested that a permeability barrier against rifampin was present in the intact organism. A type strain of
Mycobacterium smegmatis
, ATCC 607, considered resistant to rifampin also demonstrated a permeability barrier. The possibility that rifampin resistance in naturally occurring strains of mycobacteria and variable levels of resistance in strains of certain species of this organism are due to permeability barriers is discussed.
Rapid Microbiological Assay for Chlorhydroxyquinoline That Uses a Cryogenically Stored Inoculum
Authors: Cosgrove R. F.
Published: June 2012

A rapid microbiological assay for chlorhydroxyquinoline is described. It is a turbidimetric procedure that uses
Streptococcus faecalis
as the test organism. Results are available within 5 h. Data are presented to show the advantages of using a cryogenically stored inoculum over an inoculum prepared on a daily basis.
Clavulanic Acid: a Beta-Lactamase-Inhibiting Beta-Lactam from
Streptomyces clavuligerus
Authors: Reading C. , Cole M.
Published: June 2012

A novel β-lactamase inhibitor has been isolated from
Streptomyces clavuligerus
ATCC 27064 and given the name clavulanic acid. Conditions for the cultivation of the organism and detection and isolation of clavulanic acid are described. This compound resembles the nucleus of a penicillin but differs in having no acylamino side chain, having oxygen instead of sulfur, and containing a β-hydroxyethylidine substituent in the oxazolidine ring. Clavulanic acid is a potent inhibitor of many β-lactamases, including those found in
Escherichia coli
(plasmid mediated),
Klebsiella aerogenes, Proteus mirabilis
, and
Staphylococcus aureus
, the inhibition being of a progressive type. The cephalosporinase type of β-lactamase found in
Pseudomonas aeruginosa
and
Enterobacter cloacae
P99 and the chromosomally mediated β-lactamase of
E. coli
are less well inhibited. The minimum inhibitory concentrations of ampicillin and cephaloridine against β-lactamase-producing, penicillin-resistant strains of
S. aureus, K. aerogenes, P. mirabilis
, and
E. coli
have been shown to be considerably reduced by the addition of low concentrations of clavulanic acid.
Cephradine Penetration into Cerebrospinal Fluid and Effects of Its Administration into the Cerebral Ventricles of Cats
Authors: Harik Sami I. , Akl Kamal F. , Uwaydah Marwan
Published: June 2012

In cats that had high, sustained serum concentrations of cephradine, penetration of the drug into the cerebrospinal fluid (CSF) was poor. Serum cephradine levels were, on the average, 100-fold higher than the CSF levels. On the other hand, the direct injection of cephradine into the lateral cerebral ventricles of cats yielded high CSF cephradine concentrations without evidence of central nervous system toxicity.
Semiautomated Turbidimetric Bioassay for the Ionophore A23187
Authors: Westhead J. E.
Published: June 2012

The inhibitory effect of A23187 against
Staphylococcus aureus
was used to quantitate the activity of this ionophore in fermentation samples and in isolation and crystallization samples. The assay was shown to be rapid and reproducible.
In Vitro Studies of Netilmicin, a New Aminoglycoside Antibiotic
Authors: Stewart Dorothy , Bodey Gerald P. , LeBlanc Barbara
Published: June 2012

Netilmicin, a semisynthetic derivative of sisomicin, was tested in vitro against 600 clinical bacterial isolates. At a concentration of 1.56 μg/ml, over 90% of gram-negative bacilli were inhibited. Netilmicin was substantially more active against isolates of
Serratia marcescens
and
Enterobacter
spp. than gentamicin, sisomicin, tobramycin, or amikacin. Isolates of
Staphylococcus aureus
(both penicillin G susceptible and resistant) were quite susceptible to netilmicin. Most isolates of
Klebsiella
spp. and
Serratia
spp. and some of the isolates of
Pseudomonas aeruginosa
that were resistant to gentamicin proved to be susceptible to netilmicin.
Response of Influenza Virus-Infected Mice to Selected Doses of Ribavirin Administered Intraperitoneally or by Aerosol
Authors: Berendt R. F. , Walker J. S. , Dominik J. W. , Stephen E. L.
Published: June 2012

The effects of graded doses of ribavirin administered either by aerosol or intraperitoneally were compared in influenza virus-infected mice. The median effective dose values (based upon percent survival) were 3.3 and 15.8 mg/kg per day for the aerosol and intraperitoneal routes, respectively. Lung lesion scores and titer of virus were lower after aerosol than intraperitoneal therapy.
Double-Osmotic-Shock Procedure to Prepare Gentamicin Adenine Mononucleotide Transferase for the Enzymatic Assay of Gentamicin
Authors: Dankert J. , Woltjes J.
Published: June 2012

The release of gentamicin adenine mononucleotide transferase during single, cold, osmotic-shock treatment of
Escherichia coli
K-12 W677/HJR66 is not always maximal. The quantity of gentamicin adenine mononucleotide transferase in osmotic extracts could be significantly increased when a double-shock procedure was performed.
Distribution of Amikacin in Serum, Muscle, and Fat in Children After a Single Intramuscular Injection
Authors: Daschner F. , Reiss E. , Engert Jürgen
Published: June 2012

Amikacin concentrations in serum, muscle, and fat were determined in 41 children after intramuscular administration of 7.5 mg/kg of body weight. At 1.5 h amikacin reached peak concentrations in serum (mean value, 14.9 μg/ml) as well as in muscle (2.2 μg/g) and fat (1.89 μg/g) tissue; from then on all concentrations declined. Amikacin concentrations exceeded 1 μg/g in muscle for at least 3 h and in fat for at least 4 h.
Production of an Antibiotic by an Organism from Human Feces
Authors: Iglewski Wallace J.
Published: June 2012

An antibiotic-producing, gram-positive, rod-shaped bacterium was isolated from an individual who often lacked coliforms and fungi in fecal samples. The cell-free antibiotic is 1,200 daltons and Pronase sensitive and was shown to have activity against some coliforms and yeast.
Penetration of Cefamandole into Spinal Fluid
Authors: Steinberg Evan A. , Overturf Gray D. , Baraff Larry J. , Wilkins Jeanette
Published: June 2012

Twelve patients, aged 6 months to 62 years, with proven bacterial meningitis, were given a single intravenous dose of cefamandole (33 mg/kg) 75 to 140 min before a routine lumbar puncture. Infecting organisms included
Haemophilus influenzae
(eight cases),
Streptococcus pneumoniae
(two cases), and
Neisseria meningitidis
and β-hemolytic streptococcus (one each). Cerebrospinal fluid (CSF) was analyzed by microbiological assay for cefamandole. The median concentration was 0.60 μg/ml, ranging from undetectable to 7.4 μg/ml. CSF cefamandole concentrations correlated with CSF protein: in six patients with CSF protein less than 100 μg/dl, the range of drug concentration was 0 to 0.62 μg/ml; and in six patients with CSF protein above 100 mg/dl, the range was 0.57 to 7.4 μg/ml. No significant correlation was noted between severity of illness, type of organism involved, or patient age and concentration of drug achieved.
Nafcillin Entry into Human Cerebrospinal Fluid
Authors: Fossieck Byron E. , Kane James G. , Diaz Carlos R. , Parker Richard H.
Published: June 2012

The entry of nafcillin into the cerebrospinal fluid (CSF) of humans was studied in the absence of meningeal inflammation. Twenty studies were performed in 18 patients receiving 40 mg of sodium nafcillin per kg intravenously over 30 min. The CSF specimens were obtained at 1, 2, 3, and 4 h postinfusion, and sera were obtained at 5 min and 1, 2, 3, and 4 h. Nafcillin was uniformly detected in the lumbar CSF at 1 h, peaked at 2 h postinfusion, and was still detectable in the CSF of three of four patients studied at 4 h.
Antiviral Activity of 3-Deazaguanine, 3-Deazaguanosine, and 3-Deazaguanylic Acid
Authors: Allen Lois B. , Huffman John H. , Cook P. Dan , Meyer Rich B. , Robins Roland K. , Sidwell Robert W.
Published: June 2012

3-Deazaguanine (ICN 4221), 3-deazaguanosine (ICN 4793), and 3-deazaguanylic acid (ICN 5412) represent a new class of synthetic guanine analogs having antiviral activity. In vitro, nine ribonucleic acid and seven deoxyribonucleic acid viruses were inhibited, including influenza, parainfluenza, rhino-, vesicular stomatitis, adeno-, herpes-, cytomegalo-, vaccinia, pseudorabies, and myxoma viruses. They were effective orally against influenza types A and B and parainfluenza type 1 (Sendai) virus infections in mice, with a therapeutic index of 16 against the latter two viruses. The course of herpes encephalitis was altered only when the drugs were applied directly into the brain. In addition, these drugs were effective inhibitors of Friend leukemia virus-induced splenomegaly in mice; treatment also produced extensions of life in these animals.
Differential Susceptibility of Spleen Focus-Forming Virus and Murine Leukemia Viruses to Ansamycin Antibiotics
Authors: Horoszewicz Julius S. , Leong Susan S. , Carter William A.
Published: June 2012

The streptovaricin complex (SvCx) and rifamycin SV derivatives display potent antiviral activity against the polycythemic strain of Friend leukemia virus (FV-P), as measured by a reduction in the number of spleen foci produced in mice. Such reductions may be explained by inactivation of functions of (i) the spleen focus-forming virus (SFFV), (ii) its “helper” murine leukemia virus (MuLV), or (iii) both viruses normally present in FV-P. We noted that preincubation of FV-P with fractionation products of SvCx, or derivatives of rifamycin SV, at low concentrations (3 to 5 μg/ml) reduces the number of spleen foci 80 to 97%, whereas titers of MuLV (from the same inoculum) remain unaffected (MuLV titers were measured by XC, S
+
L
−
, and “helper activity” assays). Our findings indicate a remarkable biological selectivity of ansamycins, as well as nonansamycin components of SvCx, against the transforming and defective spleen focus-forming virus as compared to MuLV. Thus, the drugs might be useful in distinguishing other types of oncornaviruses.
Delineation of the Relative Antibacterial Activity of Cefamandole and Cefamandole Nafate
Authors: Turner J. R. , Preston David A. , Wold J. S.
Published: June 2012

By conventional laboratory evaluation procedures, the in vitro antibacterial activities of cefamandole and its
O
-formyl ester, cefamandole nafate, appear virtually identical. When the activities of these two compounds were examined for their ability to lyse log-phase cultures of susceptible bacteria, however, cefamandole was found to be about 10 times more active than cefamandole nafate. Cefamandole nafate was shown to be rapidly converted to cefamandole in bacteriological media, with a half-life of less than 1 h at a pH of 7.0 or above. At pH 6.0, in log-phase inhibition experiments, however, cefamandole nafate is more stable, allowing delineation of the activity between cefamandole and cefamandole nafate. The efficacy of cefamandole was identical to that of cefamandole nafate in treating experimental animal infections, indicating that rapid conversion of cefamandole nafate to cefamandole occurs in vivo.
Enzymatic and Immunological Characterization of a New Cephalosporinase from
Enterobacter aerogenes
Authors: Letarte Robert , Devaud-Felix Marlyse , Pechere Jean-Claude , Allard-Leprohon Diane
Published: June 2012

A hospital strain of
Enterobacter aerogenes
(MULB 250) isolated from a urinary tract infection was found to be cephalosporin and ampicillin resistant and carbenicillin susceptible. The β-lactamase produced by this strain was extracted and purified by means of affinity chromatography, using a cephalosporin C-bound Sepharose 4B column. The purified enzyme was tested for hydrolysis of penicillin and various cephalosporins. The

K
m

value is 11.8 μM for benzyl penicillin and 130 μM for cephalosporin C. The isoelectric point of the enzyme is 9.3, and its molecular weight is 29,500 ± 1,000. Rabbit antiserum obtained against this MULB 250 β-lactamase showed no cross-reaction with other penicillinases or cephalosporinases in neutralization tests. Comparisons of results obtained with other β-lactamases, particularly from
Enterobacter cloacae
P99, indicate that the
Enterobacter
MULB 250 enzyme presents a typical cephalosporinase profile. As far as we know, this type of enzyme is relatively rare.
Antiviral Activity of Arabinosylthymine in Herpesviral Replication: Mechanism of Action In Vivo and In Vitro
Authors: Aswell J. F. , Allen G. P. , Jamieson A. T. , Campbell D. E. , Gentry G. A.
Published: June 2012

1-β-
d
-Arabinofuranosylthymine (ara-T), a metabolite of the sponge
Tethya crypta
, has shown selective activity against herpes simplex virus (HSV) replication (G. A. Gentry and J. F. Aswell, Virology
65:
294–296, 1975). Analysis of HSV-infected and uninfected cell lysates by CsCl isopycnic centrifugation showed that ara-T blocked the incorporation of [
3
H]hypoxanthine into viral deoxyribonucleic acid and, to a large extent, into host deoxyribonucleic acid of infected (but not uninfected) cells. Additional experiments with [γ-
32
P]adenosine 5′-triphosphate as a radiophosphate donor demonstrated that ara-T is phosphorylated by extracts of HSV-infected BHK cells and not by those of uninfected cells. At an ara-T concentration that almost completely inhibited the growth of LM cells, which had been transformed to a pyrimidine deoxyribonucleoside kinase
+
(dPyK
+
) phenotype by ultraviolet-inactivated HSV-1, the growth of uninfected LM cells was not affected. These results indicate that the viral dPyK is responsible for the selective antiviral activity of ara-T. This conclusion was further supported by experiments that showed that the replication of a variety of dPyK
−
mutants of HSV-1 and HSV-2 were not affected by ara-T and that ara-T inhibited the phosphorylation of deoxycytidine and deoxythymidine by HSV-1 dPyK, but not by host deoxycytidine and deoxythymidine kinases, respectively. Ara-T also selectively inhibited the replication of equine herpesvirus type 1 (EHV-1) in vitro and was effective against EHV-1 infection in vivo in hamsters. Further, EHV-1 was inhibited by ara-T and by bromodeoxyuridine in LM cells lacking a cytosol thymidine kinase, suggesting that EHV-1 induces a dPyK. Finally, spectrophotometric assay for thymine suggested that ara-T is not a substrate for nucleoside phosphorylase of hamster liver, and a microbiological assay indicated that substantial amounts of ara-T were excreted in the urine of uninfected hamsters that had received a single injection of 5 mg of ara-T, the amount given in each injection in the in vivo experiments with EHV-1.
Mode of Action of Morganocin 174
Authors: Williams J. A. , Krizsanovich-Williams K.
Published: June 2012

Morganocin 174-induced lethality was characterized by one-hit kinetics. Although it induced simultaneous inhibition of deoxyribonucleic acid, ribonucleic acid, and protein syntheses, the most striking effect of morganocin was a rapid reduction of intracellular adenosine 5′-triphosphate to less than 10% of the initial values within 2 min of addition. Accumulation of thymidine, uridine, glutamine, and proline was also inhibited. A gradual efflux of K
+
was observed, but the lethal effects of morganocin 174 could not be prevented by maintaining a high K
+
or Mg
2+
concentration. The Mor174 plasmid codes for an immunity substance that protects cells against the effect of morganocin 174.
Tolciclate: Further Antimycotic Studies
Authors: Bianchi A. , Monti G. , De Carneri I.
Published: June 2012

In vitro comparison on dermatophytes showed, on a microgram-per-milliliter basis, that tolciclate was more active than clotrimazole and miconazole in inhibiting the growth of dermatophytes in Sabouraud agar with and without 10% horse serum.
Stability of Antibiotics in Wilkins-Chalgren Anaerobic Susceptibility Testing Medium After Prolonged Storage
Authors: Zabransky R. J. , Hauser K. J.
Published: June 2012

Wilkins-Chalgren medium, when prepared in advance and stored over a 14-day period under various conditions, supported the growth of anaerobic bacteria. When antibiotics were incorporated into the medium and held under the same storage conditions, there was no detectable change in activity of the antibiotics.
Comparative Susceptibility of
Candida albicans
to Amphotericin B and Amphotericin B Methyl Ester
Authors: Bannatyne Robert M. , Cheung Rose
Published: June 2012

The in vitro antifungal activities of amphotericin B (AMB) and amphotericin B methyl ester (AME) were compared against 465 clinical isolates of
Candida albicans
. AMB and AME possessed comparable activity against half of the strains, but against the remainder of the strains the activity of AME was slightly lower than that of AMB. Rarely did AME show superior antifungal activity to AMB.
Disodium Phosphonoacetate in Cream Base as a Possible Topical Treatment for Skin Lesions of Herpes Simplex Virus in Cebus Monkeys
Authors: Palmer Amos E. , London William T. , Sever John L.
Published: June 2012

Disodium phosphonoacetate (PAA) in a cream-ointment base was applied to herpesvirus skin lesions on the genitalia of cebus monkeys. The lesions had been produced by the intradermal injection of herpes simplex virus type 2. Concentrations of 0.2, 2, and 5% PAA were used. Liberal application of PAA at concentrations of 2 and 5% proved extremely irritating and produced extensive, severe lesions over the treated area. The 2% PAA, when applied carefully to the lesion area, proved less irritating, but did not reduce healing time when compared with the placebo-treated animals. The 0.2% PAA caused slight reduction in lesion size and duration, but these differences were not statistically significant when compared with placebo-treated animals.
Differentiation of Catalases in
Mycobacterium phlei
on the Basis of Susceptibility to Isoniazid: Association with Peroxidase and Acquired Resistance to Isoniazid
Authors: Davis William B. , Phillips David M.
Published: June 2012

Mycobacterium phlei
contains two catalase activities and a single peroxidase activity. The latter is associated with one of the catalases. The single catalase-peroxidase enzyme accounted for 75% of the total catalase activity and was lost upon acquisition of resistance to the antitubercular drug isoniazid (INH). Heat-treated (68°C) wild-type cells showed similar decreases in catalase activity as well as complete loss of peroxidase activity. Catalase activity in the INH-resistant strain of
M. phlei
(Inh
r
) was unaffected by heating. The heat-sensitive catalase of the wild-type
M. phlei
was completely inhibited by 0.1 M INH, and Cu
2+
enhanced this inhibitory effect by 100-fold. No inhibition of activity was found with the heat-stable enzyme. Equivalent inhibition of catalase was also observed with nicotinic acid hydrazide and benzoic acid hydrazide. Peroxidase activity was also completely inhibited by any one of the three hydrazides, either INH, benzoic acid hydrazide, or nicotinic acid hydrazide at 10
−3
M. The presence of two catalase activities and the loss of one (catalase-peroxidase) on acquiring INH resistance or heating wild-type cells was confirmed by acrylamide gel electrophoresis of the cell-free extracts.
In Vitro Activity of Spectinomycin Against Recent Urinary Tract Isolates
Authors: Fass Robert J. , Prior Richard B.
Published: June 2012

The susceptibilities to spectinomycin of 303 recent urinary tract isolates were determined and compared to the susceptibilities of those strains to ampicillin, tetracycline, and gentamicin. Based on minimal inhibitory concentrations, 84% of
Escherichia coli, Klebsiella
, and
Enterobacter
, 31% of other
Enterobacteriaceae
, 7% of
Staphylococcus aureus
and
Streptococcus
(including enterococci), and 0% of
Pseudomonas aeruginosa
were susceptible to concentrations of spectinomycin that are easily surpassed in serum (≤32 μg/ml); 90% of all organisms tested other than
P. aeruginosa
were susceptible to concentrations that are easily surpassed in urine (≤128 μg/ml). Spectinomycin was active against more isolates than either ampicillin or tetracycline but against fewer isolates than gentamicin. Disk diffusion susceptibility tests did not reliably distinguish susceptible from resistant isolates with any of the four antibiotics studied.
Anaerobic Wound Infections in Cancer Patients: Comparative Trial of Clindamycin, Tinidazole, and Doxycycline
Authors: Klastersky J. , Husson M. , Weerts-Ruhl D. , Daneau D.
Published: June 2012

Clindamycin, tinidazole (a parent compound to metronidazole), and doxycycline were compared in vitro against 376 anaerobic bacteria isolated from clinical specimens. Bacteriostatic tests indicated that clindamycin was the most active drug, on a weight basis, against these strains except for
Clostridium
species. The three drugs were compared as therapies for anaerobic wound infections in cancer patients. In a randomized double-blind study, no statistically significant differences between clindamycin and tinidazole could be documented. Doxycycline was less active presumably because of the lack of clinical response in three out of four patients infected with doxycycline-resistant strains. No major untoward effects were observed. The bactericidal dilution of the serum was predictive of the clinical outcome.
Side Effects of Minocycline: Different Dosage Regimens
Authors: Gump Dieter W. , Ashikaga Taka , Fink Theodore J. , Radin Alan M.
Published: June 2012

The incidence of side effects due to two dosage regimens of minocycline was examined over a 5-day period. A total of 60 normal women volunteers were randomly assigned in a double-blind manner to either a group who took 100 mg of minocycline twice a day or a group who took 75 mg of minocycline twice a day for 5 days. Both groups were comparable from the standpoints of age, size, race, and the use of oral contraception, nicotine, and ethanol. They were seen on a daily basis, and symptoms were evaluated by both volunteers (from diaries) and physicians. Minocycline serum concentrations were determined on blood samples taken 2 h after the a.m. dose. Volunteers taking 150 mg of minocycline per day had significantly lower serum antibiotic concentrations than those taking 200 mg per day. However, both low- and high-dose groups exhibited similar incidence and prevalence of recorded symptoms, with the single exception of nausea, where the low-dose group had fewer symptoms than the high-dose group (
P
= 0.035). Symptomatic volunteers did not have higher serum concentrations of minocycline than their asymptomatic counterparts. When either weight or surface area was examined with antibiotic serum concentration there was a significant inverse correlation between the two on day 2 for both groups and also on day 4 for the low-dose group. It is concluded that, in women, a dose of 150 mg of minocycline per day is associated with the same degree of side effects as a dose of 200 mg per day.
Feasibility of Screening for Penicillinase-Producing
Neisseria gonorrhoeae
from Primary Culture Plates by Using a Rapid Microacidometric Test
Authors: Weissfeld Alice Schauer , Sanner Gail D. , Childress Jack R. , Dyckman John D. , Huber Thomas W. , Williams Robert P.
Published: June 2012

We have shown that it is possible to screen for penicillinase-producing
Neisseria gonorrhoeae
directly from primary culture plates. Experiments involving the cocultivation of four genera of beta-lactamase-positive (β-lac
+
) bacteria and a beta-lactamase-negative (β-lac
−
)
N. gonorrhoeae
on modified Thayer-Martin medium indicated that suppressed or inhibited β-lac
+
bacteria did not give false-positive results when isolated β-lac
−
colonies of gonococci were tested. Colonies were assayed for β-lac production by an adaptation of a microacidometric method in which bacteria could be tested before or after the addition of oxidase reagent.
Comparative Effects of Amoxycillin and Ampicillin on the Morphology of
Escherichia coli
In Vivo and Correlation with Activity
Authors: Comber K. R. , Boon R. J. , Sutherland R.
Published: June 2012

An experimental mouse intraperitoneal infection due to
Escherichia coli
was treated with subcutaneous amoxycillin or ampicillin. Specimens of blood and peritoneal washings from the infected animals were assayed for antibiotic concentrations and examined microscopically for observation of the effects produced by the two penicillins on the morphology of bacteria growing in vivo. Amoxycillin was significantly more effective than ampicillin in protecting the animals from the lethal effects of the infection, although the antibiotic concentrations in the body fluids were very similar for both compounds. However, microscopic examination showed marked differences in the morphological effects produced at equivalent dose levels by the two compounds against the bacteria present in blood and peritoneal fluid. Treatment with amoxycillin at dose levels that produced peak antibiotic concentrations in the body fluids ranging from one-quarter to three times the minimum inhibitory concentration resulted in the formation of spheroplast forms, which lysed rapidly. In contrast, at the same concentrations, ampicillin produced relatively stable filaments or long cell forms, which lysed much more slowly, although at higher dose levels the effects produced were generally similar to those seen with amoxycillin. It is concluded that the superior therapeutic activity of amoxycillin compared with ampicillin is due to its greater bacteriolytic activity in vivo.
Comparative In Vitro Activity of Five Cephalosporin Antibiotics Against Salmonellae
Authors: Strausbaugh Larry J. , Mikhail Isis A. , Edman David C.
Published: June 2012

The in vitro activities of five cephalosporin antibiotics against 121 strains of salmonellae were compared. Cefamandole and cefaclor were more potent than cefazolin, and these three drugs were more active than cephalothin and cephalexin.
Comparative Nephrotoxicity of Gentamicin and Tobramycin in Rats
Authors: Gilbert D. N. , Plamp C. , Starr P. , Bennett W. M. , Houghton D. C. , Porter G.
Published: June 2012

A rat model was utilized to compare the nephrotoxic potential of gentamicin and tobramycin. Gentamicin, 40 mg/kg per day, predictably produced renal failure and morphological evidence of proximal tubular necrosis over 14 days of treatment. An identical dosage of tobramycin was associated with only minimal morphological changes and normal concentrations of serum creatinine and blood urea nitrogen. Similar results were obtained even after the tobramycin dosage was tripled to 120 mg/kg per day. A decrease in urine osmolality, mechanism unknown, was observed in all aminoglycoside-treated rats, but the lowest osmolalities were found in the gentamicin-treated rats. According to both histological criteria and renal function measurements, gentamicin was more nephrotoxic than tobramycin in this animal model.