bluuebunny/crossref_metadata_2025 huggingface dataset:
SCE-963, a New Broad-Spectrum Cephalosporin: In Vitro and In Vivo Antibacterial Activities
Authors: Tsuchiya Kanji , Kida Makoto , Kondo Masahiro , Ono Hideo , Takeuchi Mariko , Nishi Takeshi
Published: June 2012

SCE-963 {7β-[2-(2-aminothiazol-4-yl)acetamido]-3-[({1-(2-dimethylaminoethyl)- 1H-tetrazol-5-yl}thio)methyl]-ceph-3-em-4-carboxylic acid}, a new semisynthetic cephalosporin, showed excellent antibacterial activity against gram-positive and gram-negative bacteria, including
Haemophilus influenzae
, indole-positive
Proteus, Enterobacter
species, and
Citrobacter freundii
. The minimum inhibitory concentrations of SCE-963 against most strains of clinically isolated
Escherichia coli, Klebsiella pneumoniae, H. influenzae
, and
Proteus mirabilis
were within the range of 0.2 to 0.78 μg/ml. These activities were about 10 times more potent than those of cefazolin, cephaloridine, and cephalothin. Variations in pH, addition of horse serum, and type of growth medium had no significant effect on the activity of the cephalosporin, but the inoculum size elicited a considerable effect on the activity of β-lactamase-producing strains of bacteria. SCE-963 exerted bactericidal and bacteriolytic effects on
Staphylococcus aureus
and
E. coli
. The pronounced in vitro activity was reflected in the remarkable protection in mice infected with a wide range of gram-negative bacteria, such as
E. coli, K. pneumoniae, P. mirabilis, Proteus vulgaris, Proteus morganii
, and
Proteus rettgeri
. The protective effects of SCE-963 in mice infected with
E. coli, K. pneumoniae
, and
P. vulgaris
varied according to the challenge dose. The activity of SCE-963 was far more potent when the drug was administered parenterally rather than orally.
Iontophoretic Application of Adenine Arabinoside Monophosphate to Herpes Simplex Virus Type 1-Infected Hairless Mouse Skin
Authors: Park No-Hee , Gangarosa Louis P. , Kwon Byoung-Se , Hili James M.
Published: June 2012

Several antiviral agents were applied topically or by iontophoresis to hairless mouse skin inoculated with herpes simplex virus type 1 (HSV-1), and the chemotherapeutic effectiveness was evaluated. Topical application of iododeoxyuridine, arabinoside A, and adenine arabinoside monophosphate (ara-AMP) moderately decreased the average lesion score, number of mice with paralysis, and number of mice dying in HSV-1-infected animals. Also, the mean survival time was moderately prolonged by topical application of those antiviral agents. When ara-AMP was applied by cathodal (−) iontophoresis to the HSV-1-infected skin, the average lesion score, number of mice with paralysis, and number of mice dying were greatly decreased. Furthermore, the mean survival time of mice was highly increased by cathodal (−) iontophoresis of ara-AMP. The therapeutic efficacy of ara-AMP iontophoresis was much superior to the topical application of iododeoxyuridine, arabinoside A, and ara-AMP. These data suggest that ara-AMP iontophoresis would be the method of choice for the management of HSV-1 skin lesions in hairless mice.
New Antipseudomonal Penicillin, PC-904: Affinity to Penicillin-Binding Proteins and Inhibition of the Enzyme Cross-Linking Peptidoglycan
Authors: Noguchi Hiroshi , Matsuhashi Michio , Takaoka Masayoshi , Mitsuhashi Susumu
Published: June 2012

The mechanism of action of a new antipseudomonal penicillin, PC-904, was studied with respect to its binding affinities to penicillin-binding proteins (PBPs) and its inhibitory activities on cross-linking enzymes of peptidoglycan synthesis in vitro. PC-904 showed especially high affinity (compared with that of penicillin G) to
Escherichia coli
PBP-3. It also had high affinities to PBP-2 and -1Bs and low affinities to PBP-1A, -4, -5, and -6. Similar results were obtained with
Pseudomonas aeruginosa
, in which this antibiotic showed very high affinity (compared with that of penicillin G) to PBP-3, -1A (presumably corresponding to
E. coli
PBP-1Bs), and -2; there was especially high affinity to PBP-3 and much less affinity to PBP-1B (presumably corresponding to
E. coli
PBP-1A). These results are compatible with morphological observations that at concentrations near its minimal inhibitory concentration or less, this antibiotic induced the formation of filamentous cells of
E. coli
and
P. aeruginosa
. At higher concentrations or after prolonged incubation, it induced lysis of the cells. The remarkably high affinity of PC-904 to pseudomonal PBP-3, -1A, and -2 may partly explain the potent antipseudomonal activity of this antibiotic. In
E. coli
, the concentration of PC-904 required to inhibit the cross-linking reaction in enzymatic peptidoglycan synthesis, presumably carried out by PBP-1Bs, was as low as the inhibitory concentrations of penicillin G, ampicillin, and carbenicillin.
HR 756, a Highly Active Cephalosporin: Comparison with Cefazolin and Carbenicillin
Authors: Wise R. , Rollason T. , Logan M. , Andrews J. M. , Bedford K. A.
Published: June 2012

HR 756, a new parenteral cephalosporin, was compared with cefazolin and carbenicillin for activity against a total of 264 strains of
Pseudomonas aeruginosa, Escherichia coli, Klebsiella
spp.,
Proteus mirabilis, Proteus
spp. (indole positive),
Enterobacter
spp.,
Salmonella typhi, Serratia marcescens, Providencia stuartii
, and
Staphylococcus aureus
. In every comparison, except that with the last organism, HR 756 was clearly more active than cefazolin and carbenicillin. All three compounds had similar activity against penicillin-susceptible staphylococci; against penicillin-resistant strains, HR 756 and cefazolin were equally active and superior to carbenicillin. HR 756 was compared with penicillin for activity against strains of
Streptococcus pyogenes
, Lancefield group D streptococci, and
Neisseria gonorrhoeae
; with ampicillin against
Haemophilus influenzae
; and with cefoxitin against
Bacteriodes fragilis
. HR 756 was clearly more active than the respective reference compounds in all of these comparisons, except those involving the streptococci. HR 756 and penicillin were essentially equally active against
S. pyogenes
; against Lancefield group D, penicillin was 32 times as active as HR 756. HR 756 not only compared favorably with the reference compounds with respect to relative activity, but also effected growth inhibition of essentially all test organisms (
P. aeruginosa
and group D streptococci excepted) at remarkably low concentrations ranging from 0.015 to 2.0 μg/ml. A series of seven transfers of selected strains of
E. coli, Klebsiella
spp.,
S. aureus
, and
P. aeruginosa
through medium containing HR 756 led to emergence of strains with significant levels of resistance to the agent. Resistance to HR 756 was retained for at least seven transfers through plain medium.
Cefatrizine Activity Compared with That of Other Cephalosporins
Authors: Neu Harold C. , Fu Kwung P.
Published: June 2012

Cefatrizine, a new orally administered cephalosporin, was tested against 400 clinical isolates. Cefatrizine had excellent activity against gram-positive cocci, inhibiting all except enterococci at minimal inhibitory concentrations below 1 μg/ml. Cefatrizine inhibited the majority of
Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis
, and
Salmonella
at concentrations below 12.5 μg/ml. Although cefatrizine was not hydrolyzed by many β-lactamases, it did not inhibit a number of strains of
Enterobacter, Serratia
, or indole-positive
Proteus
. Cefatrizine was more active than cephalothin or cephalexin against
E. coli, Klebsiella, Enterobacter, Citrobacter, Salmonella
, and
Shigella
. Its overall activity was less than that of cefoxitin against strains resistant to cephalothin, but its activity against cephalothin-susceptible strains was equivalent to that of cefamandole.
In Vitro Activity of Rosamicin, Josamycin, Erythromycin, and Clindamycin Against β-Lactamase-Negative and β-Lactamase-Positive Strains of
Neisseria gonorrhoeae
Authors: Biddle J. W. , Thornsberry Clyde
Published: June 2012

Randomly selected strains of β-lactamase-negative and β-lactamase-positive
Neisseria gonorrhoeae
were tested by an agar dilution method for susceptibility to rosamicin, josamycin, erythromycin, clindamycin, and penicillin G. Rosamicin was more active than erythromycin, which was more active than josamycin or clindamycin; the latter two were similar in their activity. The susceptibility to the macrolide antibiotics and clindamycin was independent of β-lactamase production, but the penicillin minimal inhibitory concentrations were higher in the β-lactamase-positive group because of the enzyme.
Strain of
Trichomonas vaginalis
Resistant to Metronidazole and Other 5-Nitroimidazoles
Authors: Meingassner Josef G. , Thurner Josefine
Published: June 2012

A strain of
Trichomonas vaginalis
(IR-78), recently isolated from a patient afflicted with recurrent symptomatic trichomoniasis, showed resistance to metronidazole, tinidazole, and nimorazole in vitro as well as in vivo. In a serial dilution test using cysteine monohydrochloride–peptone–liver infusion–maltose medium,
T. vaginalis
IR-78 was only resistant under aerobic conditions. Under anaerobic conditions it was as susceptible as the normal reference strain. The minimal lethal concentrations of metronidazole, tinidazole, and nimorazole for IR-78 were 100, 50, and 50 μg/ml aerobically and 0.4, 0.4, and 0.2 μg/ml anaérobically, respectively. The efficacy of metronidazole, tinidazole, and nimorazole was assessed in vivo by oral administration to mice simultaneously infected with IR-78 both subcutaneously and intraperitoneally. The CD
50
(dose needed to cure 50% of infections) of each compound was significantly higher for the subcutaneous than for the intraperitoneal infection. In contrast, there was little difference in CD
50
for these infections in mice inoculated with a susceptible trichomonas strain. The CD
50
's for all three compounds against intraperitoneal and subcutaneous infections with IR-78 were 2 to >70 times higher than for susceptible strain E. Both forms of infection with IR-78 could always be cured with therapeutically acceptable doses of tinidazole and nimorazole; subcutaneous infections could not be cured with tolerated doses of metronidazole.
Chloroquine Resistance in Malaria: Accessibility of Drug Receptors to Mefloquine
Authors: Fitch Coy D. , Chan Robert L. , Chevli Rekha
Published: June 2012

The process of mefloquine accumulation was studied in mouse erythrocytes infected with either
Plasmodium berghei
CS (chloroquine susceptible) or
P. berghei
CR (chloroquine resistant). In both cases, mefloquine was accumulated by a saturable process with an apparent dissociation constant of 2.5 × 10
−6
M and an apparent maximal capacity of 700 μmol per kg of erythrocyte pellet; uninfected mouse erythrocytes accumulated more than half as much mefloquine as infected erythrocytes. The process of accumulation was not stimulated by providing glucose as a substrate, and it was not inhibited in infected erythrocytes by azide, iodoacetate, or incubation at 2°C. Although mefloquine was accumulated more effectively than chloroquine by uninfected erythrocytes and by erythrocytes infected with
P. berghei
CR, competition between chloroquine and mefloquine was observed, raising the possibility that the same process of accumulation serves both drugs. Chloroquine competitively inhibits mefloquine accumulation, with an apparent inhibitor constant of 1.7 × 10
−3
M, and mefloquine competitively inhibits chloroquine accumulation, with an apparent inhibitor constant of 2 × 10
−6
M. The same process of accumulation and the same group of receptors could serve both drugs if mefloquine has greater access than chloroquine to the receptors. Regardless of whether the same process serves both drugs, undiminished accumulation by erythrocytes infected with
P. berghei
CR provides an explanation for the superiority of mefloquine in treating chloroquine-resistant malaria.
Lack of Effect of an Interferon Inducer,
N,N
-Dihexadecyl-
m
-Xylylenediamine, on Rhinovirus Challenge in Humans
Authors: Douglas R. Gordon , Waldman Robert H. , Betts Robert F. , Ganguly Rama
Published: June 2012

CP-28,888-27 and placebo nasal sprays were compared in 62 normal volunteers challenged with rhinovirus type 13 or 21 in two randomized, double-blind studies. Half of the subjects received CP-28,888-27 and half received nasal placebo administered at 24, 20, and 16 h before challenge and 4 and 8 h after challenge. In each study, the number of subjects shedding virus in nasal washes, the number developing fourfold or greater serum antibody responses, and the number developing afebrile or febrile upper respiratory tract illness were not significantly different comparing subjects given CP-28,888-27 and those given placebo. Interferon was detected in nasal washes from 5 of 15 volunteers tested in the CP-28,888-27 group compared to 2 of 15 volunteers from the placebo group.
BL-S786 (Ceforanide), a New Parenteral Cephalosporin: In Vitro Studies
Authors: Weaver Susanne S. , LeBlanc Barbara M. , Bodey Gerald P.
Published: June 2012

BL-S786 (ceforanide) is a new cephalosporin which showed broad-spectrum activity in vitro against 453 clinical isolates. At a concentration of 3.12 μg/ml, it inhibited greater than 75% of isolates of
Escherichia coli, Klebsiella
spp.,
Proteus mirabilis, Staphylococcus aureus, Streptococcus pyogenes
, and
Streptococcus pneumoniae
. Essentially no activity was observed against isolates of
Serratia marcescens
, and only minimal activity was observed against
Enterobacter
spp. Its activity was directly related to the size of the inoculum. The minimal bactericidal concentrations were similar to the minimal inhibitory concentrations for isolates of all organisms except
S. aureus
and
S. pyogenes
. The minimal bactericidal concentrations were considerably higher than the minimal inhibitory concentrations for these organisms.
Growth Curves, Microscopic Morphology, and Subcultures of Beta-Lactamase-Positive and -Negative
Haemophilus influenzae
Under the Influence of Ampicillin and Cefamandole
Authors: Yourassowsky E. , Linden M. P. Van Der , Lismont M. J.
Published: June 2012

In contrast to the results obtained with ampicillin, the minimum inhibitory concentrations of cefamandole against
Haemophilus influenzae
were within the same range (0.5 to 1.5 μg/ml) whether or not the strains were beta-lactamase producers. The minimum bactericidal concentrations were somewhat higher for beta-lactamase-positive strains (6.4 μg/ml) than for negative strains (1.2 μg/ml). In a culture with high initial microbial density, monitored by recording optical densities, the addition of 10 μg of cefamandole per ml brought about rapid lysis of a beta-lactamase-negative strain. Observation of a beta-lactamase-positive strain revealed, in the early part of the growth curve, absence of lysis and an increase of biomass similar to that observed in a drug-free control curve. In contrast to the results obtained with ampicillin, the culture consisted uniformly of spherical forms, probably in the process of division, which were capable of generating colonies. When the microbial density exposed to cefamandole was increased still further, persistent bacillary forms were observed, and after 24 h hydrolysis had eliminated every trace of microbiologically active cefamandole.
Interpretation of the Disk Diffusion Susceptibility Test for Amikacin: Report of a Collaborative Study
Authors: Washington John A. , Yu Pauline K. W. , Gavan Thomas L. , Schoenknecht Fritz D. , Thornsberry Clyde
Published: June 2012

Because excessively high rates of false resistance have been encountered with the 10-μg amikacin disk in diffusion susceptibility tests, a study was performed to examine existing zone diameter interpretative criteria and to compare the accuracy of 10- and 30-μg amikacin disks by the error rate-bounded classification scheme. Although current zone diameter interpretative criteria eliminate false susceptibles, there is an unacceptably high rate of false resistants. This problem can be resolved in most instances by revising the zone diameter interpretative criteria for the 10-μg disk (resistant, ≤9 mm; indeterminate, 10 to 11 mm; susceptible, ≥12 mm) or, preferably, by replacing the 10-μg disk with a 30-μg disk and adopting new interpretative criteria (resistant, ≤14 mm; indeterminate, 15 to 16 mm; susceptible, ≥17 mm). Because of significant differences in performance among media, it is necessary to include
Pseudomonas aeruginosa
ATCC 27853 among controls routinely tested and to exclude from use lots of Mueller-Hinton agar yielding results outside the 75% tolerance (90% confidence) limits for amikacin.
Purification of a Streptococcal Bacteriocin (Viridin B) and Its Separation from Alpha-Hemolysin
Authors: Apelgren Lynn D. , Dajani Adnan S.
Published: June 2012

Viridin B, a bacteriocin produced by
Streptococcus mitis
, copurified with the alpha-hemolysin after ammonium sulfate precipitation and gel filtration on Sephadex G-200. The bacteriocin and hemolysin were separated in some instances by ion-exchange chromatography on diethylaminoethyl-Sephadex A-50, but the two substances were shown to be distinct after polyacrylamide gel electrophoresis. Attempts at recovery of nonhemolytic or nonbacteriocinogenic mutants were unsuccessful after exposure to mutagenic agents. The molecular weight of viridin B was determined to be approximately 87,000.
Comparison of Microdilution and Broth Dilution Techniques for the Susceptibility Testing of Yeasts to 5-Fluorocytosine and Amphotericin B
Authors: Mazens Mary F. , Andrews Gail P. , Bartlett Raymond C.
Published: June 2012

Microdilution and broth dilution techniques were compared for the susceptibility testing of 50 clinical yeast isolates to 5-fluorocytosine and amphotericin B. Good correlation between methods was obtained with all isolates except
Cryptococcus neoformans
.
Pitfalls in Collecting Blood Specimens for Antibiotic Assay
Authors: Sirinavin Sayomporn , Nelson John D. , McCracken George H.
Published: June 2012

Obtaining blood samples for antibiotic analysis from intravenous lines through which the antibiotic had been administered was critically evaluated. Flushing volumes required to remove contaminating antibiotic varied with the type of antibiotic and with different plastics. Obtaining blood specimens from the intravenous lines is not practical in infants and not advised in adults.
Modification of the Colorimetric Assay for Chloramphenicol in the Presence of Bilirubin
Authors: Mason Edward O. , Kaplan Sheldon L. , Baker Carol J. , Ritter Dorothy A.
Published: June 2012

We recently found that bilirubin interferes with the colorimetric chloramphenicol assay of Kakemi et al. (K. T. Kakemi, T. Arita, and S. Ohashi, Yakugaku Zasshi 82:342–345, 1962). Levels of serum bilirubin alone (4 to 6 mg/dl) resulted in apparent concentrations of chloramphenicol which appear to be in the therapeutic range. Concentrations of serum bilirubin greater than 8 mg/dl resulted in levels of apparent chloramphenicol associated with toxicity (>50 μg/ml). Small amounts of activated charcoal added to the isoamyl acetate extraction step of the assay eliminated this interference by bilirubin.
Pharmacokinetic Determinants of Penicillin Cure of Gonococcal Urethritis
Authors: Jaffe Harold W. , Schroeter Arnold L. , Reynolds Gladys H. , Zaidi Akbar A. , Martin John E. , Thayer James D.
Published: June 2012

In a 1964 study of the pharmacokinetic determinants of penicillin cure of gonococcal urethritis, 45 male prisoner volunteers were experimentally infected with strains of
Neisseria gonorrhoeae
having known in vitro penicillin susceptibility. After developing urethritis, subjects received intramuscular penicillin G and had serum samples obtained serially to determine penicillin concentration. Using a multiple regression technique, we studied patient-associated parameters and parameters of the serum penicillin curves to determine the best predictors of treatment results. Cure was best predicted by the time the serum penicillin concentration remained above three to four times the penicillin minimum inhibitory concentration of the infecting strain (probability of correct classification, >0.80). Those cured had serum penicillin concentrations which remained in this range for means of 7 to 10 h. Our findings confirm principles of antimicrobial therapy derived from animal models and may have application in studying therapy of gonorrhea and other infectious diseases.
Treatment of Recurrent Herpes Simplex Labialis with Levamisole
Authors: Spruance S. L. , Krueger G. G. , MacCalman J. , Overall J. C. , Klauber M. R.
Published: June 2012

Because deficient immune responses may play a contributory role in recurrent herpes simplex labialis, an immunomodulating agent, levamisole, has been advocated for therapy. Forty-two patients with a high frequency of recurrent herpes simplex labialis were followed for a mean of 7.8 months (range 4 to 12) and treated for 3 days at the onset of each episode of herpes with one of three different doses of levamisole or placebo in a randomized, double-blind study. Statistical analysis revealed that as the dosage increased, so did the frequency of recurrences (
P
= 0.007). Conversely, duration of the lesions and lesion pain decreased with increasing dosage (
P
= 0.05 and 0.03). These results indicate that levamisole is not an appropriate drug for the management of recurrent herpes simplex labialis. The paradoxical response to an immunomodulator (increased frequency, decreased severity) provides evidence that altered host responses may contribute to the pathogenesis of the disease.
Rapid Antimicrobial Susceptibility Test Using Tetrazolium Reduction
Authors: Bartlett Raymond C. , Mazens Mary F.
Published: June 2012

A rapid method of antimicrobial susceptibility testing has been developed, which uses a modified microdilution procedure and an inoculum of 10
7
bacteria per ml. Results are determined within 4 h with an indicator consisting of 2(
p
-iodophenyl)-3(
p
-nitrophenyl)-5-phenyltetrazolium chloride. The precipitation of a red formazan by bacteria uninhibited by antimicrobials is accelerated by the addition of phenazine methosulfate. Isolates are classified as resistant, indeterminate, or susceptible, based on growth in up to two antimicrobial concentrations which conform closely to concentrations which correlate with the millimeter breakpoints used in the Bauer-Kirby method. Results of testing 10 antimicrobial agents against 1,126 isolates were compared with results obtained when the Bauer-Kirby method and the agar dilution procedure were used as reference methods. Enterococci were excluded because of false resistance. Discrepancies were classified as very major (false susceptibility), major (false resistance), and minor (combinations of susceptibility or resistance with indeterminate results). The rapid method versus the agar dilution method yielded 2.3% very major, 0.7% major, and 2.9% minor discrepancies, for a total of 6.0%. Of 58 organism-antimicrobial agent combinations tested, 23 displayed 1% very major discrepancies between the rapid method and the agar dilution method. Six were not therapeutically important. The remainder involved
Staphylococcus aureus, Staphylococcus epidermidis, Acinetobacter
sp., and most organisms tested with chloramphenicol. It is suggested that adjustments in antibiotic concentrations and/or inoculum size may eliminate these discrepancies. The rapid method appeared economical when compared with Autobac 1 and the Bauer-Kirby procedure.
Preliminary Studies of the Mode of Action of Arildone, a Novel Antiviral Agent
Authors: Kuhrt Michael F. , Fancher Marilyn J. , Jasty Venkatanarayana , Pancic Francis , Came Paul E.
Published: June 2012

Arildone (also known as Win 38020), a novel aryl diketone, inhibited replication of herpes simplex virus type 2 in tissue culture by interfering with an event that occurs prior to 6 h postinfection. The inhibition could be partially reversed by washing. Although the exact mechanism of action is unknown, neither viral deoxyribonucleic acid nor viral proteins were synthesized in the presence of arildone.
In Vitro Susceptibility of
Ureaplasma urealyticum
to Rosaramicin
Authors: Smith Thomas F.
Published: June 2012

Thirty-two clinical isolates of
Ureaplasma urealyticum
were inhibited by 0.036 μg of rosaramicin per ml, whereas 25 (78%) and 13 (41%) of the strains were inhibited by this concentration of minocycline and tetracycline, respectively. These results suggest that rosaramicin may be useful for the treatment of
U. urealyticum
infections.
Morphological Changes of
Escherichia coli
Induced by Bicyclomycin
Authors: Someya Akira , Tanaka Kenji , Tanaka Nobuo
Published: June 2012

Electron microscopic studies with
Escherichia coli
revealed that bicyclomycin inhibits septum formation and converts the cells to filamentous forms. The antibiotic induced high undulation and numerous blebs of the outer membrane. Sometimes cytoplasmic contents leaked into the lumen of the bleb through a disrupted region of the membrane. Breakage of the outer membrane or blebs led to cell lysis. Electron-dense masses of amorphous material and vesicles were found in the cytoplasm.
Effect of 5-Iodo-5′-Amino-2′,5′-Dideoxyuridine on Varicella-Zoster Virus In Vitro
Authors: Iltis Jeffrey P. , Lin Tai-Shun , Prusoff William H. , Rapp Fred
Published: June 2012

The antiviral effect of the nucleoside analog 5-iodo-5′-amino-2′,5′-dideoxyuridine (AIU) was tested with three isolates of varicella-zoster virus (VZV). AIU concentrations of 10 to 800 μM (3.5 to 288 μg/ml) reduced the number of plaques produced by VZV-infected cells and cell-free VZV from approximately 30 to 95%. Smaller plaque size was also observed in the presence of AIU. AIU was less effective than arabinofuranosylthymine in reducing VZV-induced plaques since as little as 5 μg of arabinofuranosylthymine per ml completely blocked plaque formation by cell-free VZV. Toxicity assays with human diploid embryo fibroblast cells were also carried out. Drug concentrations as high as 800 μM were not toxic to human diploid embryo fibroblast cells as determined by radiolabeling of cell deoxyribonucleic acid, ribonucleic acid, and protein.
Ampicillin Dosage in Bacterial Meningitis with Special Reference to
Haemophilus influenzae
Authors: Greene G. R. , Overturf G. D. , Wehrle P. F.
Published: June 2012

Ampicillin remains the preferred drug for most cases of bacterial meningitis, including those due to
Haemophilus influenzae
type b. A prospective study was performed comparing high (400 mg/kg per day)- and low (150 mg/kg per day)-dosage regimens of ampicillin in the treatment of 172 patients with bacterial meningitis. Response to both regimens was equivalent in terms of average hospital stay, duration of ampicillin therapy, microbiological response, and death and residua. Patients with
H. influenzae
infections treated with low-dosage regimens had slightly prolonged febrile courses. This study suggests that high-dosage regimens of ampicillin offer no benefit over low-dosage regimens in the treatment of bacterial meningitis.
Pharmacokinetics of
E
-5-(2-Bromovinyl)-2′-Deoxyuridine in Mice
Authors: de Clercq E. , Descamps J. , de Somer P. , Barr P. J. , Jones A. S. , Walker R. T.
Published: June 2012

The pharmacokinetics of the newly developed anti-herpes agent,
E
-5-(2-bromovinyl)-2′-deoxyuridine, was compared with that of the standard anti-herpes drug 5-iodo-2′-deoxyuridine. Both compounds were administered to mice at 100 mg/kg by either the intraperitoneal, subcutaneous, or oral route. The active blood drug levels achieved by
E
-5-(2-bromovinyl)-2′-deoxyuridine were considerably higher than those attained by 5-iodo-2′-deoxyuridine (serum peak concentrations: 40 to 100 and 4 to 10 μg/ml, respectively). Active blood drug levels could still be found 320 min after oral administration of
E
-5-(2-bromovinyl)-2′-deoxyuridine.
Inhibition by Ethambutol of Mycolic Acid Transfer into the Cell Wall of
Mycobacterium smegmatis
Authors: Takayama Kuni , Armstrong Emma L. , Kunugi Keith A. , Kilburn James O.
Published: June 2012

Ethambutol simultaneously inhibited the transfer (presumably via mycolyl acetyl trehalose) of mycolic acids into the cell wall and stimulated the synthesis of trehalose dimycolates of
Mycobacterium smegmatis
. Structural similarities of the drug and mycolyl acetyl trehalose suggested that competitive inhibition was involved.
Limited effect of trimethoprim-sulfamethoxazole prophylaxis on Pneumocystis carinii
Authors: Hughes W T
Published: June 2012

Trimethoprim-sulfamethoxazole has been proven effective in the treatment and prevention of Pneumocystis carinii pneumonitis in lower animals and humans. How effective the drug combination is in eradicating P. carinii from the host is not known. The immunosuppressed rat model was used to determine whether or not trimethoprim-sulfamethoxazole effectively eradicated the organism. Animals treated with trimethoprim-sulfamethoxazole for as long as 6 weeks were then placed in individual isolator cages, immunosuppressed with prednisone for 12 weeks, and sacrificed. P. carinii was found in the lungs of at least 90% of the drug-treated as well as untreated control groups. The data indicate that trimethoprim-sulfamethoxazole has a limited rather than a lethal effect on P. carinii and that protection is afforded only during the period of trimethoprim-sulfamethoxazole administration.
Anaerobic infection in cancer patients: comparative evaluation of clindamycin and cefoxitin
Authors: Klastersky J , Coppens L , Mombelli G
Published: June 2012

Clindamycin and cefoxitin with or without gentamicin were administered to cancer patients having localized infections presumably caused by anaerobic pathogens. The rates of favorable response were 89% in patients receiving clindamycine alone and 78% in patients receiving cefoxitin alone. When the total experience is considered (clindamycin or cefoxitin with and without gentamicin), 20 of 24 patients (83%) responded to clindamycin and 18 of 22 (82%) responded to cefoxitin. Both therapies were well tolerated. Clindamycin was found to be more effective than cefoxitin in eradicating the offending anaerobic pathogens from the site of infection. Aerobic pathogens were frequently isolated along with anaerobes from the infectious sites in this series; their susceptibility or resistance to clindamycin or cefoxitin did not influence the therapeutic response.
Use of covalently closed circular deoxyribonucleic acid for prescreening for antitumor compounds
Authors: Mong S , Strong J E , Bush J A , Crooke S T
Published: June 2012

The interactions of PM-2 deoxyribonucleic acid (DNA) with 20 known antineoplastic agents were studied using agarose gel electrophoresis and fluorescence assay systems. Actinomycin D and adriamycin (and all other anthracyclines studied) induced superhelical conformational changes in PM-2 DNA. Bleomycin A2, tallysomycin, neocarzinostatin, macromomycin, and hedamycin degraded PM-2 DNA under various conditions. The potential utility of PM-2 DNA as an antitumor antibiotic prescreening tool was further studied by examining the effects of 200 broths on PM-2 DNA employing both fluorescence and agarose gel electrophorectic assays. The assays were shown to be sensitive and rapid and to provide information not provided by other prescreens with which the PM-2 DNA assays were compared.
Virucidal activity of retinal
Authors: Reinhardt A , Sands J A , Snipes W
Published: June 2012

Herpes simplex virus type 2 and simian virus 40 were rapidly inactivated by retinal at micromolar concentrations. Other fat-soluble vitamins, particularly vitamin A derivatives, were also active against herpes simplex virus type 2 and several lipid-containing bacteriophages.
Comparative nephrotoxicity of SCH 21420 and amikacin in rats
Authors: Rankin L I , Luft F C , Yum M N , Sloan R S , Dinwiddie C B , Isaacs L L
Published: June 2012

The nephrotoxic potentials of the new aminoglycoside SCH 21420 and amikacin were compared in a rat model. Groups of rats received 100, 200, 300, or 600 mg of either drug per kg per day for 14 days. Enzymuria, urine osmolality, protein excretion, and blood urea nitrogen were monitored at periodic intervals, whereas creatinine clearance and pathological changes were determined at sacrifice. Amikacin caused more enzymuria at the two lower doses as well as greater proteinuria and blood urea nitrogen elevations at the highest dose than did SCH 21420 (P less than 0.05). Pathological changes were more severe with amikacin than with SCH 21420 at the three lower doses (P less than 0.05); however, at the 600 mg/kg per day dose, the pathological scores and creatinine clearances of animals receiving either drug were not significantly different (P greater than 0.05).
Oral neomycin dosage schedules for suppression of ammonia production by bowel flora
Authors: Suh B , Stephens J L , Kunin C M
Published: June 2012

To better define a minimal but optimal dose of oral neomycin to suppress ammonia production by bowel flora, several dosage regimens were examined in normal healthy volunteers. Fecal urease activity was quantitatively determined and was used as an indirect measure of intrinsic ammonia production by bowel flora. Large doses of neomycin were found to exert inhibition of fecal urease for many days. There was considerable variation in enzymatic activity among subjects even after adjustments were made for protein content of the stool. Depending on the dose, there was a 1- to 3-day lag in neomycin effect on stool urease activity and several days of continued effect. The most effective regimen of those studied was a loading dose of 6 g of neomycin given in three divided doses on day 1, followed by 1 g twice daily.
Biosynthetic pathway leading to gentamicin C2b
Authors: Lee B K , Nagabhushan T L , Condon R G , Shimonaski G , Kalyanpur M G , Patel M , Waitz J A
Published: June 2012

Incubation of Micromonospora purpurea SC 1210 (NRRL 5467) with L-[methyl-14C]methionine yielded [methyl-14C]gentamicin A and methyl-14C-labeled antibiotic JI-20A in a molar radioactivity ratio of 9:2. We did not isolate methyl-14C-labeled gentamicin X2, which was expected as an intermediate based on the biosynthetic pathways proposed by others. Addition of methyl-14C-labeled antibiotic JI-20A to M. purpurea SC 1124 (NRRL 8102) yielded [methyl-14C]-gentamicin C1a and [methyl-14C]gentamicin C2b in variable molar radioactivity ratios. These data do not support the biosynthetic pathway leading to gentamicin C2b proposed by Testa and Tilley.
Clinical evaluation of mezlocillin
Authors: Thadepalli H , Rao B
Published: June 2012

The safety and efficacy of intravenous mezlocillin were determined in 25 patients with aerobic, anaerobic, and mixed infections. Included were pleuropulmonary, urinary tract, skin, and soft-tissue infections, osteomyelitis, and abdominal and breast abscess. Nineteen patients (76%) were cured without recurrence as determined by clinical and bacteriological parameters. In three, the infection recurred (12%); two patients failed (8%), and in one, it was indeterminate (4%). No serious adverse effects were noted except for severe thrombophlebitis in three (12%) patients. Our preliminary data suggest that mezlocillin is a safe (except for thrombophlebitis) and effective antibiotic in the treatment of aerobic anaerobic, and mixed infections.
LY127935, a new beta-lactam antibiotic, versus Proteus, Klebsiella, Serratia, and Pseudomonas
Authors: Flournoy D J , Perryman F A
Published: June 2012

One hundred eight clinical isolates of Proteus, Klebsiella, Serratia, and Pseudomonas spp. were tested in vitro against LY127935, cefamandole, cefoxitin, ticarcillin, carbenicillin, gentamicin, tobramycin, and amikacin by broth microdilution. The activities of LY127935 were greater than or equal to those of the other antimicrobial agents against Proteus vulgaris, Klebsiella pneumoniae, and Serratia marcescens. Inhibitions were greatest, however, for ticarcillin and carbenicillin versus Proteus morganii and gentamicin versus Pseudomonas aeruginosa.
Mezlocillin pharmacokinetics in patients with normal and impaired renal functions
Authors: Bergan T , Brodwall E K , Wiik-Larsen E
Published: June 2012

The pharmacokinetics of intravenous bolus doses of 1.0 g of mezlocillin were studied in 13 persons with normal and reduced renal functions. In renal failure a moderate increase was observed for the terminal serum half-life(t1/2 beta). This changed from a mean of 1.1 h at a glomerular filtration rate of 100 ml/min to 1.6 h at 10 ml/min. The difference was not statistically significant. The excretion of unchanged drug in urine during 24 h was reduced from a mean of 59.4% (range, 52 to 77) in subjects with glomerular filtration rate above 50 ml/min to 10% (range, 7.9 to 12.1) in two patients with glomerular filtration rate of 10 to 20 ml/min. The volume of distribution during the beta-phase, Vd,b, was 14% of the body weight. Much of the antibiotic was metabolized, and this proportion increased upon reduction in renal function.
Variability in the susceptibility pattern of Bacteroides fragilis in four Detroit area hospitals
Authors: Bawdon R E , Rozmiej E , Palchaudhuri S , Krakowiak J
Published: June 2012

Recent clinical isolates of Bacteroides fragilis selected at random from four Detroit area hospitals were collected over a 3-month period, and the minimum inhibitory concentrations were determined within several days. The levels of antimicrobial agents used in this survey breached the concentration attainable in the patient's serum. The antimicrobial susceptibility patterns of these isolates to five antimicrobial agents suggest that there is a 20% variation in the resistance to clindamycin and also up to 20% variation among the other four antibiotics in the four area hospitals. The changing susceptibility pattern of B. fragilis to antibiotic resistance suggests that minimum inhibitory concentrations should be determined for all isolates from serious clinical infections.
Effect of azacytidine on Simian Virus 40 nucleoprotein complexes
Authors: Johnson-Thompson M , Rosenthal L J
Published: June 2012

Simian virus 40 nucleoprotein complexes synthesized in the presence of 5-azacytidine showed small differences in sedimentation rate on neutral sucrose and buoyant density in metrizamide and cesium chloride. Simian virus 40 deoxyribonucleic acid (DNA) I, isolated from the nucleoprotein complexes of drug-treated cultures, was found to band at a higher buoyant density and therefore had a decreased ability to bind ethidium bromide. The data indicated that these molecules were deficient in superhelical turns. Treatment with 5-azacytidine was shown to inhibit protein synthesis, which preceded the inhibition of DNA synthesis. Under the same conditions, protein synthesis was inhibited to a greater degree and occurred much faster than inhibition of DNA syntheses. Upon removal of the drug, resumption of protein and DNA synthesis occurred slowly. It is concluded that the inhibition of simian virus 40 DNA synthesis and the conformational alterations in DNA I isolated from nucleoprotein complexes result from the inhibition of protein synthesis.
Kinetic studies on enzymatic acetylation of chloramphenicol in Streptococcus faecalis
Authors: Nakagawa Y , Nitahara Y , Miyamura S
Published: June 2012

The kinetics of chloramphenicol (CP) acetylation by CP acetyltransferase from Streptococcus faecalis was studied. CP was shown to be acetylated enzymatically to its 3-O-acetyl derivative (3-AcCP) in the presence of acetyl coenzyme A, after which 3-AcCP was converted nonenzymatically to its 1-O-acetyl isomer, 1-O-acetyl CP (1-AcCP). At equilibrium, the 1-AcCP and 3-AcCP were present in a 1:4 ratio. Subsequently the diacetylated product, 1,3-O-O-diacetyl CP [1,3-(Ac)2CP], was enzymatically produced from 1-AcCP by the same enzyme. Theoretical calculation of rate constants (k1, k2, k3) for each successive reaction is as follows: (Formula: see text). This calculation gave k1 = 0.4 min-1, k2 = 0.002 min-1, and k3 = 0.016 min-1. Experimental results agreed closely with these calculated values.
In vitro antibacterial activity of cefoperazone (T-1551), a new semisynthetic cephalosporin
Authors: Matsubara N , Minami S , Muraoka T , Saikawa I , Mitsuhashi S
Published: June 2012

Cefoperazone, a new semisynthetic cephalosporin, has a broad spectrum of antibacterial activity. It is as active as cefazolin and cefamandole against gram-positive bacteria and is more active than cefazolin and cefamandole against such gram-negative bacilli as Escherichia coli, Klebsiella pneumoniae, Proteus species, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae, and Serratia marcescens. The superiority of cefoperazone over cefazolin and cefamandole with respect to activity against P. aeruginosa by more than 200-fold was especially remarkable. As with other beta-lactam antibiotics, there was only a small spread between the minimum inhibitory concentrations and the minimum bactericidal concentrations of cefoperazone and a significant decrease in activity with an increase in inoculum size. Activity was not altered significantly by the addition of human serum to the test medium. Cefoperazone is relatively stable to hydrolysis to beta-lactamases produced by gram-negative bacteria. Relative rates of hydrolysis of cefoperazone by cephalosporinases are 7.0 to 0.01, with reference to cephaloridine hydrolysis (base, 100). Cefoperazone is also more stable than penicillin G and cephaloridine to various types of penicillinases.
Clavulanic acid and penicillin treatment of Staphylococcus aureus renal infection in mice
Authors: Heerema M S , Musher D M , Williams T W
Published: June 2012

Clavulanic acid, an inhibitor of beta-lactamase, was used together with penicillin to treat infection caused by a penicillinase-producing Staphylococcus aureus. Clavulanic acid + penicillin administered to mice, prophylactically or in treatment of established infection, reduced morbidity, bacterial counts in the kidneys, and/or mortality; these differences were statistically significant when compared with those obtained by using penicillin or clavulanic acid alone.
Fortimicin A: collaborative in vitro susceptibility. Comparison with amikacin and gentamicin against 11,840 clinical bacterial isolates
Authors: Jones R N , Barry A L , Fuchs P C , Gavan T L , Sommers H M , Gerlach E H
Published: June 2012

The susceptibility of 11,840 clinical bacterial isolates to fortimicin A was determined by agar dilution or broth microdilution methods and compared with their susceptibility to amikacin and gentamicin. In general, the in vitro activity of fortimicin A was essentially the same as that of amikacin. Significant exceptions were the increased effectiveness of fortimicin A against Serratia marcescens and the greater activity of amikacin against Pseudomonas and other nonfermentative gram-negative bacilli. On a weight-for-weight basis, gentamicin showed greater activity than the other two antimicrobial drugs against most species; S. Marcescens was the major exception. However, at concentrations equivalent to achievable nontoxic serum levels, the proportion of isolates inhibited by the three drugs was quite comparable. There were several strains with unusually high resistance to one or more of the tested antibiotics. These usually occurred in one of the six participating institutions and could be traced to specific enzyme-producing or permeability mutants endemic to that particular institution.
Amikacin pharmacokinetics in pediatric patients with malignancy
Authors: Cleary T G , Pickering L K , Kramer W G , Culbert S , Frankel L S , Kohl S
Published: June 2012

The pharmacokinetics of amikacin were evaluated in 50 pediatric patients (1 to 17 years of age) with malignancies and normal renal function. Dosage regimens of 5 mg/kg per dose were administered intravenously (i) over 30 min every 8 h, (ii) over 60 min every 8 h, and (iii) over 60 min every 6 h. Administration of amikacin over 30 min produced concentrations in serum of 29.3 +/- 5.7 micrograms/ml at the end of the infusion and subtherapeutic concentrations 4 h after the infusion. The regimen of 20 mg/kg per 24 h, divided into doses given every 6 h infused over 60 min, achieved concentrations in serum at the end of the infusion of 17.2 +/- 1.7 micrograms/ml and at 6 h of 1.2 +/- 0.3 microgram/ml. The serum half-life was 1.24 +/- 0.09 h, volume of distribution was 0.26 +/- 0.02 liter/kg, and total body clearance rate was 131 +/- 10 ml/min per 1.73 m2. No accumulation of amikacin was noted, and no significant side effects could be attributed to the drug. This study suggests that the optimal initial dosage regimen of amikacin in children is 20 mg/kg per 24 h administered in equal doses every 6 h over 60 min; however, optimal therapy requires individualization of dosage based on measured serum concentrations and susceptibility data on bacterial pathogens isolated.
Effect of cefamandole nafate on blood coagulation and platelet function
Authors: Custer G M , Briggs B R , Smith R E
Published: June 2012

Platelet function and coagulation were tested after brief in vivo exposure to cefamandole nafate and in the presence of various concentrations of the drug in vitro. Alterations in hemostatic function were observed only with exposure to drug concentrations severalfold higher than those expected to prevail clinically.
Pyran and Polyribonucleotides: Differences in Biological Activities
Authors: Morahan Page S. , Regelson William , Munson Albert E.
Published: June 2012

Maleic anhydride-divinyl ether copolymer (pyran) and the polyribonucleotides are both large polyanions with potent antiviral activity. However, they are biologically quite different. Interferon levels of 100 units or more/ml were associated with antiviral activity of polyribonucleotides. Interferon induction by pyran compounds was not primarily involved in antiviral resistance because preparations that did not induce interferon possessed antiviral activity equal to that of interferoninducing preparations. Both polyriboinosinic-cytidylic acid [poly (rI.rC)] and pyran increased the immune response to sheep erythrocytes in the Jerne hemolytic plaque-forming cell (PFC) assay, but their modes of immunoadjuvant action differed. On peak day, poly (rI.rC)-treated mice demonstrated 5.1 × 10
4
PFC/spleen (557 PFC/10
6
nucleated cells) and pyran-treated mice exhibited 4.5 × 10
4
PFC/spleen (299 PFC/10
6
nucleated cells), as compared with 2.7 × 10
4
PFC/spleen (261 PFC/10
6
nucleated cells) in controls. The compounds also differed in phagocytic alteration; polyribonucleotides did not affect phagocytosis whereas pyran produced a biphasic response. Both polyanions exhibited toxic inhibition of liver microsomal enzyme metabolism of type I and type II drugs. However, whereas pyran sensitized mice 50-fold to the lethal effects of endotoxin, the polyribonucleotides did not significantly sensitize mice to endotoxin.
Antibiotics from
Pseudomonas reptilivora
I. Taxonomic Classification and Optimal Conditions of Fermentation for Antibiotic Production
Authors: Rio Luis A. Del , Olivares J. , Blesa M. C. , Mayor F.
Published: June 2012

A bacterium able to produce wide-spectrum antibiotic substances was isolated from a plant extract. The antibiotic-producing bacterium was identified as
Pseudomonas reptilivora
after suitable morphological and biochemical assays. Optimal yield conditions for antibiotic production in liquid medium have been established.
In Vitro Activity of Tobramycin and Gentamicin
Authors: Britt Michael R. , Garibaldi Richard A. , Wilfert James N. , Smith Charles B.
Published: June 2012

The in vitro antimicrobial activity of tobramycin and gentamicin was compared against 362 bacterial isolates. The minimal inhibitory concentration (MIC) of tobramycin was fourfold less than the MIC of gentamicin against most of 119
Pseudomonas
organisms. Gentamicin and tobramycin had similar in vitro activity against
Enterobacteriaceae
and
Staphylococcus aureus. Proteus rettgeri
were commonly resistant to both tobramycin and gentamicin. The 10-μg tobramycin disc separated resistant (MIC ≥5 μg/ml) and susceptible (MIC <5 μg/ml) organisms in 359 of 362 tested. In disc diffusion testing, the tobramycin and gentamicin zone diameters were found to vary significantly with concentrations of magnesium ions in the media employed. The MIC of tobramycin varied with the size of the inoculum, and tobramycin was most effective at a neutral
p
H.