bluuebunny/crossref_metadata_2025 huggingface dataset:
Chloramphenicol Pharmacokinetics in Hospitalized Patients
Authors: Koup Jeffrey R. , Lau Alan H. , Brodsky Barbara , Slaughter Richard L.
Published: June 2012

The apparent body clearance of chloramphenicol was investigated in 21 hospitalized adult patients on 27 occasions. Apparent body clearance was found to be significantly lower (1.99 ± 1.49 ml/min per kg) in patients with total serum bilirubin concentrations of >1.5 mg/100 ml than in patients with serum bilirubin concentrations of ≤1.5 mg/100 ml (3.57 ± 1.72 ml/min per kg;
P
< 0.001). Serum protein binding of chloramphenicol was lower in cirrhotic patients (42.2 ± 6.8% bound) than in normal adults (53.1 ± 5.2% bound;
P
< 0.001). Low binding of chloramphenicol was also found in the serum of premature neonates (32.4 ± 8.2% bound;
P
< 0.001). Reduced binding in neonates implies the need for a lower therapeutic range of total chloramphenicol concentration (3.5 to 13.9 μg/ml) compared with the usual adult range (5 to 20 μg/ml). Finally, three case reports are presented which demonstrate marked abnormalities and intrasubject variation in chloramphenicol clearance.
Antifolate Activity of Isoaminopterin in HeLa Cells
Authors: Rosemond-Hornbeak Hortencia , Nair M. G.
Published: June 2012

The antifolate activity and the transport characteristics of isoaminopterin (IA) in HeLa cells were studied and compared with those of methotrexate (MTX). Both IA and MTX inhibited the incorporation of [2-
14
C]deoxyuridine into HeLa cell DNA by 50% at a concentration of 0.09 μM by 8 h postaddition of the compounds. Unlike MTX, the inhibition of DNA synthesis by IA was time dependent and reached a maximum at 24 h. IA-induced inhibition was due to interference with folate metabolism, since it could be completely reversed with N
5
-formyl-tetrahydrofolate. Competitive transport experiments between IA and either radiolabeled MTX or radiolabeled folate showed that IA preferentially uses the reduced folate/MTX transport system. IA inhibited MTX uptake by 50% at a concentration of 6.8 μM but had a negligible effect on folate transport.
Comparative Susceptibility of
Haemophilus
Species to Cefaclor, Cefamandole, and Five Other Cephalosporins and Ampicillin, Chloramphenicol, and Tetracycline
Authors: Watanakunakorn Chatrchai , Glotzbecker Cheryl
Published: June 2012

The minimal inhibitory concentration of cefaclor, cephalexin, cephradine, cefamandole, cephalothin, cephapirin, cefazolin, ampicillin, chloramphenicol, and tetracycline for inhibition of 198 freshly isolated clinical strains of
Haemophilus
species (23
H. influenzae
type b, 157
H. influenzae
non-type b, 14
H. parainfluenzae
, and 4
H. aphrophilus
) was determined simultaneously by a slightly modified WHO-ICS agar dilution method. Nine strains were resistant to ampicillin. There was no correlation between ampicillin resistance and minimal inhibitory concentration of other antibiotics. All strains were susceptible to chloramphenicol, and all except five were susceptible to tetracycline. Cefaclor was the most active oral cephalosporin, and cefamandole was the most active parenteral cephalosporin. Among the seven cephalosporins tested, cefamandole was the most effective compound. All but two strains were inhibited by cefamandole at 2 μg or less per ml.
Isoniazid Inhibition of the Synthesis of Monounsaturated Long-Chain Fatty Acids in
Mycobacterium tuberculosis
H37Ra
Authors: Davidson Leslie A. , Takayama Kuni
Published: June 2012

Isoniazid inhibited C
24
and C
26
monounsaturated fatty acid synthesis in
Mycobacterium tuberculosis
H37Ra. Time courses of this inhibition and that of mycolic acid synthesis were similar.
Comparative In Vitro Activity of Five Cephalosporins Against Lactobacilli
Authors: Bayer Arnold S. , Chow Anthony W. , Concepcion Nelydia F. , Guze Lucien B.
Published: June 2012

Of five parenteral cephalosporins tested against 43 lactobacilli, cephaloridine, cefazolin, and cefamandole were the most active inhibitory and bactericidal agents. Timed-kill analysis revealed a slow bactericidal effect, with significant declines in mean minimal bactericidal concentration values at 48 h versus 24 h.
Susceptibility of
Campylobacter fetus
subsp.
jejuni
to Twenty Antimicrobial Agents
Authors: Walder Mats
Published: June 2012

One hundred recent clinical isolates of
Campylobacter fetus
subsp.
jejuni
were tested by an agar dilution technique for susceptibility to each of 20 antimicrobial agents. Doxycycline and gentamicin were the most active of the drugs examined, inhibiting all strains at concentrations achievable in serum. Although the median minimal inhibitory concentration of erythromycin was low, 8% of the isolates were highly resistant. All isolates of
Campylobacter fetus
subsp.
jejuni
were relatively resistant to the β-lactam antibiotics. Some strains were highly resistant to metronidazole and tinidazole.
Chloramphenicol Bioassay
Authors: Bannatyne Robert M. , Cheung Rose
Published: June 2012

An accurate plate diffusion bioassay for chloramphenicol is described, in which the fast-replicating
Beneckea natriegens
and 1.5% salt agar are used. Zones of inhibition were well defined after 3 h, and the limit of sensitivity of the method was around 2 μg/ml. The concurrent presence of gentamicin did not influence the assay. The assay is simple to carry out and duplicate assays can be performed with as little as 100 μg of capillary blood.
Human Fibroblast Interferon for Clinical Trials: Pharmacokinetics and Tolerability in Experimental Animals and Humans
Authors: Billiau Alfons , De Somer Piet , Edy Victor G. , De Clercq Erik , Heremans Hubertine
Published: June 2012

Human fibroblast interferon (F-interferon) purified by adsorption on controlled-pore glass was given intramuscularly to patients at daily dosages of up to 20 × 10
6
units. Serum levels of antiviral activity were low or undetectable. In contrast, reasonably high serum titers were found in patients receiving interferon prepared from leukocytes (L-interferon). Similarly, in rabbits lower serum titers were seen with F-interferon than with L-interferon. These results are at variance with those obtained earlier (V. G. Edy, A. Billiau, and P. De Somer, J. Infect. Dis.
133:
A18–A21, 1976). Possible explanations for this discrepancy are discussed. The F-interferon evoked febrile reactions, delayed skin reactivity, and transitory lymphopenia in humans. Some patients developed an allergic state of the reaginic type as evidenced by a weal and flare reaction after intradermal challenge. However, these patients did not show allergic symptoms after intramuscular injections. None of the side effects was severe enough to prohibit continuation of the treatment; most of them seemed to be due to contaminants not removed by the purification method. The possibility is considered that some of the side effects, e.g., delayed skin reactivity, are sufficiently specific to justify identification of the active principals.
Effects of Fildes Enrichment on Antibiotic Susceptibility Testing of
Haemophilus influenzae
in the Autobac
Authors: Robinson David B. , Schell Ronald F. , LeFrock Jack L. , Chan John K.
Published: June 2012

The results of this investigation showed that the Autobac could be used to determine the susceptibility of
Haemophilus influenzae
to ampicillin, chloramphenicol, and tetracycline when eugonic broth was supplemented with 1.5% Fildes enrichment. An excellent correlation was obtained between the susceptibilities as determined by the agar dilution minimal inhibitory concentration method and the Autobac. For ampicillin all
H. influenzae
isolates with minimal inhibitory concentrations of ≤1 μg/ml had light scattering indexes of ≥0.60. Those isolates with minimal inhibitory concentrations of ≥4 μg/ml had light scattering indexes of ≤0.49. For chloramphenicol and tetracycline all isolates had minimal inhibitory concentrations of ≤1 μg/ml and light scattering indexes of ≥0.71.
Diffusion Disk Susceptibility Testing with Cefotaxime
Authors: Aswapokee Nalinee , Aswapokee Prasit , Neu Harold C. , Fu Kwung P.
Published: June 2012

The diffusion disk susceptibility of
Staphylococcus aureus, Enterobacteriaceae
, and
Pseudomonas aeruginosa
to cefotaxime was determined. A 30-μg disk provided data for the susceptibility of
P. aeruginosa
, but yielded extremely large zones of inhibition against
Enterobacteriaceae
. A 5-μg disk seemed to provide the most useful susceptibility data for
S. aureus
and
Enterobacteriaceae
.
Clinical and Bacteriological Evaluation of Cefoxitin Therapy in Children
Authors: Jacobson Jay A. , Santos Jose I. , Palmer W. Martin
Published: June 2012

Cefoxitin, a parenteral cephamycin β-lactam antibiotic, was evaluated for safety and efficacy in children with bacterial infections other than meningitis. Twentysix patients between 3 months and 7 years of age were treated with 80 to 160 mg/kg per day. The most common diagnoses were cellulitis (13 patients), pneumonia (5 patients), and bone and joint infection (4 patients). Nine patients were bacteremic. The most frequently recovered pathogens were
Staphylococcus aureus
(six patients),
Haemophilus influenzae
(four patients), and
Streptococcus pneumoniae
(three patients). All organisms were susceptible to cefoxitin. All 26 children were considered improved or cured. No severe adverse reactions were encountered. Phlebitis (4%), eosinophilia (12%), and elevated liver function tests (4%) were associated with therapy. Cefoxitin appears to be a safe, effective, and well-tolerated antibiotic when used in children with susceptible bacterial infections other than meningitis.
Importance of Medium in Demonstrating Penicillin Tolerance by Group B Streptococci
Authors: Kim Kwang Sik , Yoshimori Robert N. , Imagawa David T. , Anthony Bascom F.
Published: June 2012

A total of 30 clinical isolates of group B streptococci were studied for penicillin tolerance in vitro. Minimal inhibitory and bactericidal concentrations of penicillin were determined simultaneously in three test media which have been used for group B streptococci, tryptose phosphate, Mueller-Hinton, and Todd-Hewitt broths, using a logarithmic-phase inoculum of 10
5
colony-forming units per ml. Minimal inhibitory concentrations in the three media did not differ significantly. However, minimal bactericidal concentrations were significantly higher in tryptose phosphate broth (mean, 1.04 μg/ml) than in Mueller-Hinton broth (0.22 μg/ml) or Todd-Hewitt broth (0.15 μg/ml). Similarly, ratios of minimal bactericidal to minimal inhibitory concentrations were significantly greater in tryptose phosphate broth than in Mueller-Hinton or Todd-Hewitt broth. After incubation in tryptose phosphate broth for an additional 24 h, the minimal bactericidal concentration consistently fell to levels which were only twice or equal to the minimal inhibitory concentration. This study illustrates the importance of the medium in the demonstration of penicillin tolerance and of controlling laboratory variables in the susceptibility testing of group B streptococci with penicillin.
Decrease of Drug Resistance in
Salmonella
in The Netherlands
Authors: van Leeuwen W. J. , van Embden J. , Guinée P. , Kampelmacher E. H. , Manten A. , van Schothorst M. , Voogd C. E.
Published: June 2012

Since 1974, tetracycline resistance in salmonellae of human and porcine origin has decreased nation-wide in The Netherlands. This decrease has coincided with the ban on incorporation of tetracycline in animal feeds.
Australian evaluation of Autobac I with suggested interpretive and technical modifications
Authors: Funnell G R , Guinness M D
Published: June 2012

Autobac I, a recently introduced semiautomated method for rapid antibiotic susceptibility testing, has been evaluated by comparison with the calibrated dichotomous sensitivity disk diffusion technique, which is routinely used in many Australian hospitals. Only the most common clinical isolates, Staphylococcus aureus, Escherichia coli, Klebsiella sp., and Proteus mirabilis, were included in this evaluation, and an overall interpretive agreement of 93% was obtained. However, an unusually high rate of discrepancy was noted in several organism-antibiotic combinations, in particular E. coli and P. mirabilis with ampicillin, S. aureus with penicillin, and methicillin-resistant S. aureus with methicillin, erythromycin, and clindamycin. The discrepancies associated with ampicillin have been reduced from 29 and 24% for E. coli and P. mirabilis, respectively, to less than 5% after the utilization of commercial 10-micrograms diffusion disks, in preference to the lower antibiotic content disks supplied by the Autobac manufacturer. Furthermore, modifications in the interpretive procedure have eliminated discrepancies associated with S. aureus and penicillin.
Aflatoxin inhibition of viral interferon induction
Authors: Hahon N , Booth J A , Stewart J D
Published: June 2012

The inhibitory effect of four basic aflatoxins on interferon induction by influenza virus in LLC-MK2 cell monolayers follows a structure-activity series with decreasing potency in the order aflatoxin B1 greater than G1 greater than B2 approximately G2. Of the four aflatoxins, B1 was the most deleterious to both cell growth and the viability of cells in confluent cultures. The fact that higher levels of influenza virus growth were attained in aflatoxin-treated cells than in normal cell monolayers was related to increased aflatoxin concentration in association with decreased interferon production. The ability of interferon to confer cellular resistance against viral infection, however, was not altered by aflatoxin. The inhibitory activity of aflatoxin on interferon production may be a factor contributing to impairment of host resistance to viral infections.
In vitro response of Enterobacter to ampicillin
Authors: Lampe M F , Minshew B H , Sherris J C
Published: June 2012

Three strains of Enterobacter were studied for their response to ampicillin. They exhibited a basic level of resistance that depended on the medium used and high-level mutational resistance at a frequency of 10(-5) to 10(-7). Two classes of mutants were selected, one of which showed markedly enhanced antibiotic inactivation as indicated by a biological assay and the other of which resembled the wild type in this regard. Both mutants showed cross-resistance to other beta-lactam antibiotics. The results explained discrepancies between traditional broth dilution minimum inhibitory concentration tests and early read automated procedures.
Effect of inoculum size on the susceptibility of Haemophilus influenzae b to beta-lactam antibiotics
Authors: Syriopoulou V P , Scheifele D W , Sack C M , Smith A L
Published: June 2012

The current prevalence of ampicillin-resistant Haemophilus influenzae b meningitis requires accurate knowledge of susceptibility to alternative antibiotics. One variable affecting susceptibility is inoculum size. We studied the susceptibility of 200 clinical isolates of H. influenzae b to ampicillin, carbenicillin, and cefamandole at inocula of 10(5) and 10(7) CFU by two techniques. Fifty ampicillin-susceptible and fifty ampicillin-resistant strains were tested for susceptibility to ampicillin by broth dilution while 100 of each were tested by agar dilution. An inoculum effect was found, being greatest with the ampicillin-resistant strains. The range of minimal inhibitory concentrations for the resistant strains was 25 to 800 microgram of ampicillin per ml at an inoculum of 10(5) and 2,000 to less than 6,000 microgram of ampicillin at 10(7); 1.0 to 150 microgram of carbenicillin per ml at 10(5) and 6.2 to 2,000 microgram of carbenicillin per ml at 10(7); 0.4 to 2.0 microgram of cefamandole at 10(5) and 1.0 to 125 microgram/ml at 10(7). Because of this inoculum effect, we would not recommend the use of carbenicillin or cefamandole for therapy of ampicillin-resistant H. influenzae meningitis.
Ceftizoxime (FK 749), a new parenteral cephalosporin: in vitro and in vivo antibacterial activities
Authors: Kamimura T , Matsumoto Y , Okada N , Mine Y , Nishida M , Goto S , Kuwahara S
Published: June 2012

FK 749 is a new parenteral cephalosporin derivative which is more active against various gram-negative bacilli, including the opportunistic pathogens such as Enterobacter, Citrobacter species, and Serratia marcescens, than cephalosporins and cephamycins such as cefotiam, cefamandole, cefuroxime, cefotaxime, and cefmetazole. FK 749 was especially active against gram-negative organisms resistant to these related antibiotics. FK 749 was more potent in bactericidal activity than the other antibiotics, and the activity was clearly enhanced in the presence of 90% defibrinated rabbit blood. The therapeutic effect of subcutaneously injected FK 749 in mice infected with various gram-negative bacilli was far superior to that of cefotiam, cefamandole, cefuroxime, and cefmetazole and was almost the same as that of cefmetazole in mice infected with Staphylococcus aureus and that of ticarcillin in mice infected with Pseudomonas aeruginosa. FK 749 has, in general, nearly the same in vitro and in vivo antibacterial activities as cefotaxime. The former had more potent bactericidal activity in the presence of the blood than the latter and showed more excellent therapeutic effect than cefotaxime against infections caused by large inoculum sizes.
Antibiotics and suppression of lymphocyte function in vitro
Authors: Banck G , Forsgren A
Published: June 2012

The effects on the mitogenic response of human T lymphocytes were studied for 20 different antibiotics. No apparent inhibitory effect could be detected for penicillins, cephalosporins, aminoglycosides, chloramphenicol, sulfamethoxazole, trimethoprim, nalidixic acid, and 5-fluorocytosine. There were effects at high concentrations with erythromycin, clindamycin, and rifampin, and these antibiotics could also be shown to depress the mitogenic response of B lymphocytes. With fusidic acid, nitrofurantoin, and doxycycline there was an inhibiting effect at low concentrations on the mitogenic responses of B and T lymphocytes and on in vitro antibody production. Protein synthesis in unstimulated lymphocytes was also inhibited. Some antibiotics thus may impair the function of human lymphocytes in vitro.
Inactivation of beta-lactam antibiotics by Legionella pneumophila
Authors: Fu K P , Neu H C
Published: June 2012

Beta-lactam-inactivating activity has been found in all sero-groups of Legionella pneumophila. The beta-lactamase activity could be detected in intact cells and released by ethylenediaminetetraacetic acid treatment, indicating that it is located in the periplasmic space. The enzyme acted primarily as a cephalosporinase hydrolyzing cefamandole, cephalothin, cephaloridine, and also penicillin G and ampicillin. Cefoxitin and cefuroxime were not hydrolyzed. Clavulanic acid and CP-45,899, beta-lactamase inhibitors, prevented the hydrolysis of cephalosporins and penicillins. The beta-lactamase activity appears to be different from that found in Enterobacteriaceae and Pseudomonas.
Ineffectiveness of erythromycin for treatment of Haemophilus vaginalis-associated vaginitis: possible relationship to acidity of vaginal secretions
Authors: Durfee M A , Forsyth P S , Hale J A , Holmes K K
Published: June 2012

To assess the efficacy of oral erythromycin in the treatment of nonspecific vaginitis (NSV), conducted a nonrandom, unblinded pilot study among 17 women with symptoms and signs of NSV. At the completion of treatment, 10 of 13 patients had persistent symptoms, 9 of 13 had persistent abnormal discharge, and 11 of 13 had persistently positive cultures for Haemophilus vaginalis. Ten patients with persistent or relapsing NSV and four who did not complete erythromycin treatment were retreated with oral metronidazole, and 14 of 14 showed clinical improvement and eradication of H. vaginalis. The susceptibility of 27 clinical isolates of H. vaginalis to erythromycin was determined at pH 5.5, 6.0, 6.5, and 7.0. The minimal inhibitory concentration of erythromycin for H. vaginalis was approximately 10-fold higher at pH 5.5 than at pH 7.0. Erythromycin is not effective for the treatment of H. vaginalis-associated NSV; this may be partly attributable to the reduced activity of this drug in acidic vaginal secretions.
Susceptibility and Synergy Studies of Methicillin-Resistant
Staphylococcus epidermidis
Authors: Ein Michael E. , Smith Nedra J. , Aruffo John F. , Heerema Mark S. , Bradshaw Major W. , Williams Temple W.
Published: June 2012

Methicillin-resistant
Staphylococcus epidermidis
is an important cause of cerebrospinal fluid shunt infections and prosthetic valve endocarditis. Agar dilution minimum inhibitory concentrations were determined for 100 strains of methicillin-resistant
S. epidermidis
which were isolated from clinical specimens. Vancomycin inhibited all 100 strains at ≤3.12 μg/ml, whereas clindamycin inhibited only 46 strains at ≤12.5 μg/ml. Methicillin-resistant
S. epidermidis
strains were resistant to achievable levels of erythromycin, with 90 strains having a minimum inhibitory concentration of ≥3.12 μg/ml. Of the five cephalosporins and one cephamycin tested, cefamandole was the most active in vitro, inhibiting 97 strains at ≤25 μg/ml. Antibiotic synergism was examined by a quantitative bacterial time-kill method. Synergism (≥10
2
kill by the combination over the most effective single antibiotic at 24 h) was demonstrated with vancomycin (1.56 μg/ml) plus cefamandole (6.25 μg/ml) in 14 of 14 strains, vancomycin plus cephalothin (6.25 μg/ml) in 14 of 14 strains, vancomycin plus rifampin (0.008 to 0.012 μg/ml) in 6 of 12 strains, rifampin plus cefamandole in 9 of 12 strains, and rifampin plus cephalothin in 10 of 12 strains. The emergence of populations of bacteria resistant to 0.2 μg of rifampin per ml developed in three of five methicillin-resistant
S. epidermidis
strains tested. The addition of either vancomycin, cephalothin, or cefamandole to the rifampin prevented the emergence of resistance in these three strains. Clinical trials of synergistic antibiotic combination therapy for serious methicillin-resistant
S. epidermidis
infections are indicated.
Miconazole therapy for treatment of fungal infections in cancer patients
Authors: Jordan W M , Bodey G P , Rodriguez V , Ketchel S J , Henney J
Published: June 2012

The effectiveness of miconazole was evaluated in 37 documented fungal infections, 32 of which were major infections. All patients were receiving therapy for advanced malignancy, with 28 patients having acute leukemia. The overall cure rate was 41% and it was also 41% for major fungal infections. Nine of 22 patients with Candida albicans infections were cured, and 3 of 11 patients with Candida tropicalis infections were cured. A total of 183 patients who received miconazole for presumed or documented fungal infection were evaluated for toxicity. Nausea and vomiting and central nervous system toxicity were the most common side effects, occurring in 25 and 16% of the patients, respectively. Overall, the drug was tolerated well, with only four patients requiring the drug to be permanently discontinued because of toxicity.
Evaluation of gentamicin and penicillin as a synergistic combination in experimental murine listeriosis
Authors: Edmiston C E , Gordon R C
Published: June 2012

The administration of a combination of penicillin and gentamicin to mice given an intraperitoneal challenge of a highly pathogenic strain of Listeria monocytogenes resulted in increased survival as compared with groups receiving penicillin alone or gentamicin alone or a control group that received no antibiotic. The median survival of animals that eventually died was no longer than in groups receiving single antibiotics and suggests that additional studies should be carried out to further investigate the possibility of synergism in animal models.
Studies with a Hydrophobic, Spin-Labeled Virucidal Agent
Authors: DeLuca Neal , Keith Alec , Snipes Wallace
Published: June 2012

A spin-labeled virucidal agent was synthesized, purified, and tested for its activity against the enveloped bacterial virus φ6 and herpes simplex virus. This compound, designated BPN, inactivated greater than 99% of φ6 and herpes simplex virus in vitro at concentrations as low as 0.1 mM. Detailed studies were carried out on the mechanism of inactivation of φ6 by BPN. These studies revealed that treatment of φ6 by BPN specifically removes a single envelope protein that is considered to be responsible for adsorption of the virus to the host cell. Related experiments with the φ6 host,
Pseudomonas phaseolicola
strain HB10Y, showed that this organism is insensitive to the effects of BPN. The basis for the differential sensitivity of φ6 to BPN, in comparison to the host cell, was investigated by electron spin resonance techniques. It was found that, for φ6, HB10Y, and their extracted phospholipids, BPN is localized in the hydrocarbon zones of the membrane bilayer. However, in the case of φ6, the rotational mobility of BPN is much reduced in comparison to that in HB10Y and the phospholipid preparations. Furthermore, an Arrhenius plot of rotational correlation time (τ
c
) showed a marked discontinuity in slope at 31°C in the case of φ6, but not for the other samples studied. This suggests a strong interaction between the φ6 envelope proteins and the lipid domains in which BPN is localized. Calculations based on the known lipid and protein composition of φ6 indicate that there is an absence of “free-lipid” pools in the viral envelope. It is suggested that BPN localizes in free-lipid pools of cell membranes, where its presence is of little or no consequence, but that in φ6 the BPN perturbs the hydrophobic interactions between phospholipids and proteins in the envelope.
Effect of treatment with 1-beta-D-arabinofuranosylthymine of experimental encephalitis induced by herpes simplex virus in mice
Authors: Machida H , Ichikawa M , Kuninaka A , Saneyoshi M , Yoshino H
Published: June 2012

1-beta-D-Arabinofuranosylthymine (ara-T) was examined for its therapeutic efficacy against encephalitis in mice inoculated intracerebrally with herpes simplex virus. Intraperitoneal treatment with 100 mg of ara-T per kg twice daily for 4.5 days was as effective as treatment with 50 mg of arabinosyladenine 5'-monophosphate per kg. Under the same conditions, doses of 5-iododeoxyuridine or arabinosylcytosine (50 mg/kg each) were not effective. Even when the virus inoculum was as high as 320 or 3,200 50% lethal doses, ara-T increased the life span significantly. Oral treatment with 27 mg of ara-T per kg produced a modest increase in the mean survival time, equal to that of 50 mg of ara-T per kg administered intraperitoneally or subcutaneously. A single dose of ara-T, 800 mg/kg intraperitoneally or 400 mg/kg orally, was effective. The 50% lethal dose of ara-T administered intraperitoneally and that administered orally were more than 10 and 15 g/kg, respectively. The therapeutic indexes (maximal tolerated dose divided by minimal effective dose) in multiple intraperitoneal treatments and in multiple oral treatments were estimated to be more than 25 and 100, respectively.
CI-867, a new semisynthetic penicillin: in vitro studies
Authors: Weaver S S , Bodey G P
Published: June 2012

CI-867, a new semisynthetic penicillin, has exhibited broad-spectrum activity in vitro against gram-positive cocci, except penicillin G-resistant Staphylococcus aureus, and against gram-negative bacilli. It was especially active against Pseudomonas aeruginosa and as active as mezlocillin and piperacillin against Klebsiella pneumoniae. CI-867 was bactericidal against most organisms. Its activity was greatly reduced when the inoculum was increased from 10(5) to 10(7) organisms per ml.
Antifungal Properties of Polymyxin B and Its Potentiation of Tetracycline as an Antifungal Agent
Authors: Schwartz S. N. , Medoff G. , Kobayashi G. S. , Kwan C. N. , Schlessinger D.
Published: June 2012

High concentrations of polymyxin B inhibited the growth of
Candida albicans
and
Saccharomyces cerevisiae
. When these yeasts were incubated with concentrations of polymyxin B too low to affect growth, and were then exposed to tetracycline, protein synthesis was inhibited and at least 99% of the organisms were killed. Neither inhibition of protein synthesis nor cell death occurred in cultures treated with high concentrations of tetracycline alone. We conclude that polymyxin B at high concentrations affects the cell membrane of yeasts, which results in inhibition of growth. At low concentrations, it increases the permeability of the yeast cell membrane to tetracycline, which then inhibits protein synthesis and leads to cell death.
Disposable Plastic Tray for Large Plate Assays of Antibiotics
Authors: Rønsted P.
Published: June 2012

A new disposable plastic tray for large plate assays of antibiotics was compared with conventional trays with plate-glass bottoms, and was found to be entirely satisfactory.
Improved Experimental Model for Measuring Skin Degerming Activity on the Human Hand
Authors: Michaud R. N. , McGrath M. B. , Goss W. A.
Published: June 2012

A gloved-hand method is presented for evaluating the interaction of antimicrobial agents with the normal resident bacterial flora of human skin. One of the key features of the experimental model is a simplified technique for sampling the skin, which involves the addition of eluting fluid to the gloved hand. As with other skin sampling techniques, the number of bacteria recovered from the hands showed considerable variation from subject to subject. However, no significant differences were observed between the numbers of bacteria recovered from the right and left hands of individual subjects. The mean number of bacteria recovered from the hand before and after washing with nonmedicated soap was consistent and reproducible over a period of at least 5 consecutive days. The number of recoverable bacteria from the hand was greatly reduced by a single treatment with a surgical scrub preparation containing hexachlorophene. The extent of skin degerming achieved was little affected by the use of a surgical brush, and was maximal at approximately 30 min after contact with the hexachlorophene-containing formulation. It was determined that the level of transient bacteria on the hands could be controlled by a simple wash with nonmedicated soap, resulting in a stabilized base-line level from which treatment interactions with the resident microflora could be measured more precisely. The basic elements of the method presented fulfill the requirements of a satisfactory experimental model for the in vivo evaluation of skin-degerming agents on the hand. The selection of appropriate experimental designs allows treatment comparisons to be made with a high degree of statistical confidence.
Antibiotic Susceptibility Testing of
Bacteroides
Authors: Bodner Stanley J. , Koenig M. Glenn , Treanor L. Lockie , Goodman Jay S.
Published: June 2012

Seventy
Bacteroides
strains isolated from clinical materials were tested in vitro against nine antibiotics by means of modified disc diffusion and agar dilution tests. Correlating the agar dilution susceptibility with the concentrations achievable in serum for each drug tested, we found that at least 90% of the strains were susceptible to clindamycin, chloramphenicol, carbenicillin, and lincomycin. Only 40% were susceptible to tetracycline. Except for tetracycline and chloramphenicol, the disc diffusion technique exhibited inadequate predictive value in terms of “susceptibility” and “resistance” for the
Bacteroides
strains tested.
Evaluation of a Computer-Associated Electronic Zone Analyzer in Single-Disc Antimicrobial Susceptibility Testing
Authors: Moellering Robert C. , Mercier Bettie A. , Kunz Lawrence J. , Poitras James W.
Published: June 2012

A computer-associated electronic zone analyzer was evaluated for use in measuring zones of inhibition for single-disc antimicrobial susceptibility testing. This unit gave measurements which were reproducible and comparable to those obtained by the standard manual technique. By feeding results directly into the computer, this system eliminates errors in interpretation of zone sizes and in transcription of results to clinical reports. It has also been shown to eliminate possible sources of observer bias. In routine high-volume use, this system has resulted in a substantial saving of man-hours of work.
Effect of Isoprinosine Against Influenza and Some Other Viruses Causing Respiratory Diseases
Authors: Muldoon Robert L. , Mezny Linda , Jackson George G.
Published: June 2012

The antiviral activity of isoprinosine was tested in tissue cultures and mice. In tissue cultures, concentrations of 25 to 100 μg/ml inhibited the infectivity of influenza and herpes hominis viruses but not parainfluenza virus, rhinovirus, or adenovirus. Among different strains of influenza A, there was considerable variability in the inhibitory concentration of isoprinosine. For influenza B, a zone effect was observed in the inhibitory drug concentration. Oral prophylactic administration of isoprinosine beginning 24 hr before infection with an intermediate challenge dose of influenza A and continued as treatment for 5 days produced a significant reduction in mortality. No protection was provided against a high dose challenge. Oral or intraperitoneal treatment of mice beginning 24 hr after infection with influenza A or B viruses significantly delayed or prevented death when the drug was administered for 10 days, but not when treatment was limited to 4 days. An increased fatality rate which occurred in treated mice given a virus dose of low lethality could not be attributed to drug toxicity.
Activity of Methacycline, Related Tetracyclines, and Other Antibiotics Against Various L-Forms and Their Parent Bacteria In Vitro
Authors: Hubert E. G. , Kalmanson G. M. , Montgomerie J. Z. , Guze L. B.
Published: June 2012

The activity of methacycline against microbial L-forms and their parent bacteria was compared with that of oxytetracycline, chlortetracycline, tetracycline, and demethylchlortetracycline, as well as with that of 22 other antibiotics which included examples of major groups of antibiotics. The L-forms and bacteria used were
Streptococcus faecalis, S. faecium, S. faecalis
var.
zymogenes, Staphylococcus aureus
(three strains),
Proteus mirabilis
(two strains),
Pseudomonas aeruginosa, Escherichia coli
(two strains),
Sarcina flava, Serratia marcescens
, and
Klebsiella pneumoniae
. The five tetracyclines had similar activities and were more active against L-forms than bacterial forms, except that the bacterial form of
S. flava
was more susceptible than the L-form. In general, other antibiotics (except the penicillins) were more active against L-forms than bacterial forms. There were certain exceptions where the bacterial form was more susceptible than the L-form. These included the effect of polymyxin B and colistin on
P. aeruginosa, E. coli
, and
P. mirabilis
, and the effect of gentamicin on
P. aeruginosa, E. coli, S. flava
, and
S. marcescens
.
Simple Photometric Assay of β-Lactamase Activity
Authors: Zyk Naomi
Published: June 2012

A simple photometric assay of β-lactamase activity was developed. The method is based on a decrease in optical density at 620 nm caused by the formation of a penicilloic acid-iodine complex. The enzymatic reaction is instantaneously stopped by the addition of a concentrated iodine-tungstate solution. Data showing the time and concentration dependence of the reaction are presented. By varying both the time of the assay and the concentration of the enzyme, substrates of widely different
V
max
values could be assayed. The assay is compared with other methods of determining β-lactamase activity.
Quality Control of Antimicrobial Disc Susceptibility Testing with a Rapid Method Compared to the Standard Methods
Authors: Barry A. L. , Fay G. D. , Atchison F. W.
Published: June 2012

A rapid method for assay of antimicrobial agents in human serum was modified to provide a method for rapidly assessing the activity of antimicrobial discs being used for susceptibility testing. Each morning, discs are taken from the clinical laboratory's working supply and are applied directly onto test plates which have been inoculated, preincubated, and stored in a refrigerator. Inhibitory zones can be measured within 5 to 6 hr, i.e., before that day's batch of tests is to be set up. If the zone of inhibition for any agent is more than 2 standard deviations below the mean, the discs are discarded and another cartridge is selected from the stock supply for that day's susceptibility tests. In this way, discs of questionable potency are discarded before they are used for testing, rather than waiting until the next day as is usually done with the standard methods. The rapid control test yields zones which are slightly smaller and somewhat more variable than with the standard Kirby-Bauer or agar overlay methods, but the slight decrease in precision is outweighed by the advantages of rapidity and simplicity.
Antimicrobial Activity of a Series of Halo-Nitro Compounds
Authors: Bowman W. R. , Stretton R. J.
Published: June 2012

Sec-α-halo-nitro compounds are active antibacterial and antifungal agents, and the sec-bromo derivatives are the most active and stable.
Role of the membrane potential in bacterial resistance to aminoglycoside antibiotics
Authors: Damper P D , Epstein W
Published: June 2012

The electrical potential difference (delta psi) across the membrane of Escherichia coli was measured by the distribution of lipid-soluble cations and correlated with resistance to dihydrostreptomycin, where resistance is presumed due to reduced uptake of the drug. A good correlation between the two measured parameters was found under all conditions tested, which included effects of several mutations, inhibitors, changes in pH, and osmolarity. The most dramatic changes were seen when pH was varied; in wild-type strains resistance increased more than 100-fold, and delta psi fell by 70 mV when pH was reduced from 8.5 to 5.5. These results were interpreted as support for a model in which the uptake of the polycationic aminoglycosides is electrogenic and therefore driven by delta psi. The factor common to mutations and conditions which increase resistance was a reduction in delta psi. A simple model was developed which relates the minimal inhibitory concentration to the rate of aminoglycoside uptake and the rate of growth.
In vitro activity of cefbuperazone against anaerobic bacteria
Authors: Wexler H , Carter W T , Harris B H , Finegold S M
Published: June 2012

The in vitro activity of cefbuperazone was compared with that of cefoxitin, moxalactam, and piperacillin against 305 strains of anaerobic bacteria. Piperacillin was the most active overall, inhibiting 97% of all anaerobes tested at 128 micrograms/ml. Cefbuperazone had poor activity against the Bacteroides fragilis group and Clostridium difficile (43 and 0% susceptible, respectively) but good activity (90.5%) against all other anaerobic bacterial species tested.
Passicol, an Antibacterial and Antifungal Agent Produced by
Passiflora
Plant Species: Preparation and Physicochemical Characteristics
Authors: Birner J. , Nicolls Joan M.
Published: June 2012

An increased yield of the crude material with antibacterial and antifungal activity produced by
Passiflora
species was obtained by aerated bathing of cut rinds of banana passion fruit in water in rotating cylindrical bottles. The crude material was separated into several fractions by thin-layer chromatography with the use of silica gel and ethyl acetate-chloroform (2:1). The fractions showing ultraviolet absorption maxima in the vicinity of 340, 358, and 375 to 377 nm were biologically active. The data indicate that the active material, here called “Passicol” for the first time, has characteristics of the polyacetylenic group of compounds. The activity can be preserved for a long time when crude material is stored in organic solvent in the dark at 6 C. Gentle bathing of the cut rinds of
Passiflora
in water in the presence of air and ethylene stimulated the formation of the active principle.
Phenazopyridine-Sulfonamide Combination Antibacterial Therapy in Mice
Authors: Heifetz C. L. , Fisher M. W.
Published: June 2012

Phenazopyridine, at its maximum tolerated dose, did not affect the effectiveness of sulfonamides against uropathogenic bacterial species in mice.
Renal Handling and Lymph Concentration of Two Cephalosporin Analogues, Cephacetrile and Cephaloridine: an Experimental Study in Dogs
Authors: Naber Kurt G. , Madsen Paul O.
Published: June 2012

Cephacetrile (CIBA 36′ 278-Ba) and cephaloridine (both cephalosporin derivatives) were compared in dogs with regard to their possible nephrotoxicity, renal handling, and concentration in the renal lymph. No adverse acute effect of either drug on the glomerular filtration rate and effective renal plasma flow was found at very high concentrations in the plasma, with or without concomitant administration of a potent diuretic (furosemide). Cephaloridine was filtered only by the kidney, whereas there was evidence that cephacetrile was also excreted by tubular secretion at low concentrations. The renal lymph concentration of the two antibiotics (in the hilar as well as the capsular lymph vessels) was found to be significantly lower than the simultaneous arterial plasma concentrations. When concentrations in the plasma were high, the relative lymph concentrations of cephaloridine and cephacetrile were in the same range as those of iothalamate (70 to 90% of the arterial plasma level), whereas at low plasma concentrations the lymph concentration of cephacetrile was markedly lower, a finding possibly explained by the active tubular secretion of cephacetrile.
In Vitro Susceptibility of
Neisseria gonorrhoeae
to Spectinomycin Examined by a Broth Dilution Method
Authors: Levy J. , Wicher K. , Rose N. R.
Published: June 2012

The in vitro susceptibility of 113 strains of
Neisseria gonorrhoeae
to spectinomycin was determined by the broth dilution method and was compared with their susceptibility to penicillin and ampicillin. All strains demonstrated a susceptibility to spectinomycin in a range between 2.5 and 20 μg/ml; 96% of these strains were susceptible in a range from 5 to 10 μg/ml. The same strains were susceptible to ampicillin at concentrations between 0.06 and 0.5 μg/ml and to penicillin between 0.02 and 1.25 units/ml. For the majority of strains, the minimal inhibitory and bactercidal concentrations were identical; however, with more than 10% of the strains, the minimal inhibitory concentration was lower than the minimal bactericidal concentration.
Bromomonamycins, Unnatural Analogues of the Monamycin Cyclodepsipeptide Antibiotics: Production, Isolation, and Biological Activity
Authors: Hall M. J. , Handford B. O. , Hassall C. H. , Phillips D. A. S. , Rees A. V.
Published: June 2012

Growth of
Streptomyces jamaicensis
in a low-chloride medium supplemented with NaBr resulted in the biosynthesis of brominated analogues of the natural chlorinated monamycins. Purification of these new compounds was undertaken by Craig countercurrent distribution studies. Diffusion and dilution assays indicated that antibiotic activity of a monamycin was inversely proportional to its unsolvated molecular weight. The bromo analogues were the least active of the series.
Permeability Control in Animal Cells by Polyenes: a Possibility
Authors: Medoff Gerald , Kwan C. N. , Schlessinger D. , Kobayashi G. S.
Published: June 2012

The polyenes amphotericin B and vitamin A enhanced the specific actions of rifampin, fusidic acid, and 1,3-bis(2-chloroethyl)-1-nitrosourea against mouse L cells in tissue culture as measured by macromolecular synthesis and cell survival.
Comparative Pharmacokinetics of BB-K8 and Kanamycin in Dogs and Humans
Authors: Cabana Bernard E. , Taggart James G.
Published: June 2012

Comparative studies in beagle dogs suggested that the pharmacokinetic profiles of BB-K8 and kanamycin are similar. After intravenous (iv) administration to dogs, BB-K8 and kanamycin were rapidly distributed in plasma and tissue fluids; their “apparent” volumes of distribution comprised approximately 23% of the total body volume. Like kanamycin, BB-K8 had a plasma half-life of about 0.8 h which paralleled the urinary excretion rate. Approximately 92% of the dose was excreted as unchanged drug within 6 h of dosing, and clearance appeared to be primarily by glomerular filtration. After intramuscular (im) administration to dogs, BB-K8 and kanamycin were totally and rapidly absorbed; peak concentrations in the plasma occurred 0.5 to 1.0 h after dosing. The kinetic parameters governing the distribution and elimination of BB-K8 and kanamycin after an im dose were similar to those obtained for iv dosing and indicate desirable dose-independent kinetics. A human pharmacokinetic study indicated that the kinetic profiles of BB-K8 and kanamycin are similar in man after im dosing. Like kanamycin, BB-K8 is rapidly absorbed, yielding peak serum concentrations of about 20 μg/ml at 1 h after a 500-mg im dose. The plasma half-life of these two drugs was approximately 2.3 h. Clearance in man was primarily by glomerular filtration, and the urinary excretion of BB-K8 and kanamycin accounted for 83% of the dose.
N,N
-Dioctadecyl-
N′,N′
-Bis(2-Hydroxyethyl) Propanediamine: Antiviral Activity and Interferon Stimulation in Mice
Authors: Hoffman W. W. , Korst J. J. , Niblack J. F. , Cronin T. H.
Published: June 2012

CP-20,961,
N,N
-dioctadecyl-
N′, N′
-bis(2-hydroxyethyl)propanediamine, is an antiviral drug with low acute toxicity in mice. Parenteral injection of this compound protected mice against lethal infections with encephalomyocarditis and Semliki Forest viruses and effectively suppressed pox formation by vaccinia infection. Maximal antiviral effects were observed when CP-20,961 was administered 6 to 12 h before infection. An interferon detected in plasma 12 to 20 h after the drug was given appeared to mediate these effects. Comparison of the minimal effective and lethal doses in mice established a therapeutic index of 300.
Increased Susceptibility of
Neisseria gonorrhoea
from a Rural Area
Authors: Gump Dieter W. , Berry Paul T.
Published: June 2012

The in vitro susceptibility of 18 to 24 isolates of
Neisseria gonorrhoea
were tested against 12 different antimicrobial agents. These isolates represent all of the gonococcal organisms which had been isolated by the bacteriology laboratory of the Vermont State Department of Health from 1 March to 31 July 1972 and originated from patients cultured in Vermont. These isolates were considerably more susceptible to penicillin G and tetracycline than are current isolates from elsewhere in the United States and Canada. Possible explanations for this difference are discussed.
Antiviral Activity and Induction of Interferon-Like Substance by Quinacrine and Acranil
Authors: Gláz E. T. , Szolgay Erika , Stöger Ivana , Tálas Margarita
Published: June 2012

Several drugs with certain structural similarities (tricyclic ring system with dialkylaminoalkyl side chains) to tilorone, a potent interferon inducer, were screened for antiviral activity in vivo. Two acridine drugs, Acranil and quinacrine, were found to be effective, the former being almost as protective as tilorone and the latter less so. Both agents induced an interferon-like substance which could be detected in the serum of treated mice. The concentration of the inhibitory factor in the serum was highest after exposure to tilorone, followed in turn by Acranil and quinacrine, based on the administration of equal weights of drugs. Both tilorone and Acranil induced lower levels of circulating interferon-like substance in Balb/c mice than in other strains of mice. The serum factor induced by Acranil was shown to be stable at pH 2.