bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of Chemotherapy and Immune Defenses in Experimental Murine Cryptococcosis
Authors: Graybill John R. , Craven Philip C. , Mitchell Linda F. , Drutz David J.
Published: June 2012

Congenitally athymic nude (nu/nu) and thymus-containing heterozygous (nu/X) mice were infected intraperitoneally with
Cryptococcus neoformans
over a wide range of challenge doses. Cryptococcal disease progressed more rapidly in nude mice than in their nu/X littermates. When nu/X mice were treated with amphotericin B, all survived an otherwise lethal dose of
C. neoformans
. At larger challenge doses, survival was prolonged in nu/nu mice treated with amphotericin B, but they later succumbed to cryptococcosis. At lower challenge doses, amphotericin B was curative in some nude mice. Therapy of nude mice with both amphotericin B and flucytosine further prolonged survival at high-dose challenge and increased the number of cures at low-dose challenge. These studies support an interaction of antifungal chemotherapy with thymus-dependent immune defense mechanisms. This interaction is most evident at high challenge doses, where antifungal chemotherapy cures nu/X mice but only modestly prolongs survival in nude mice.
Antimalarial Activities of the 4-Quinolinemethanols WR-184,806 and WR-226,253
Authors: Schmidt L. H. , Crosby Ruth , Rasco Jane , Vaughan Dennis
Published: June 2012

WR-184,806 and WR-226,253, two 4-quinolinemethanols structurally similar to WR-142,490 (mefloquine), have been studied in depth in owl monkeys infected with various drug-resistant and drug-susceptible strains of
Plasmodium falciparum
and
P. vivax
in an effort to provide support and guidance for projected evaluations in human volunteers. The results of these studies, confirmatory of preliminary appraisals, showed that WR-184,806 was approximately one-third as active as WR-142,490 against infections with a multidrug-resistant strain of
P. falciparum
, whereas WR-226,253 was twice as active. Additionally, the current studies showed: (i) that both WR-184,806 and WR-226,253 were significantly more active against infections with blood schizonts of
P. vivax
than against those of
P. falciparum;
(ii) that their activities against established infections with either
Plasmodium
species were functions of the total doses delivered, single doses being as effective as three or seven fractional doses given on successive days; (iii) that WR-184,806 could be administered intravenously as the phosphate salt and was curative via this route in single doses; and (iv) that based on comparative curative doses, WR-184,806 was slightly more active and WR-226,253 was seven times more active against infections with a multidrug-resistant strain of
P. falciparum
than was chloroquine against infections with a 4-aminoquinoline-susceptible strain.
Comparison of the In Vitro Activities of HR756 with Cephalothin, Cefoxitin, and Cefamandole
Authors: Sosna Jacob P. , Murray Patrick R. , Medoff Gerald
Published: June 2012

The in vitro activity of HR756, a new semisynthetic cephalosporin, was compared with the activities of cephalothin, cefoxitin, and cefamandole against 1,535 isolates of gram-positive and gram-negative bacteria. HR756 was less active than cephalothin and cefamandole and twofold more active than cefoxitin against
Staphylococcus
. All four of the antibiotics were inactive against the enterococcus group of
Streptococcus
; however, HR756 was the most active antibiotic against the other isolates of
Streptococcus
. HR756 was also more active against isolates of
Enterobacteriaceae
, including 84 to 95% of the isolates resistant to one or more of the other three antibiotics. HR756, at a concentration of 12.5 μg/ml, inhibited 86, 75, and 100% of the isolates of
Pseudomonas aeruginosa
, other
Pseudomonas
species, and
Acinetobacter
, respectively. The minimal inhibitory concentrations and minimal bactericidal concentrations of HR756 were within one twofold dilution for 11 of 21 gram-positive cocci and 119 of 125 gram-negative bacilli tested.
Low Trimethoprim Susceptibility of Anaerobic Bacteria Due to Insensitive Dihydrofolate Reductases
Authors: Then Rudolf L. , Angehrn Peter
Published: June 2012

All the 28
Bacteroides fragilis
strains investigated were susceptible to sulfamethoxazole (minimal inhibitory concentration < 16 μg/ml) and resistant to trimethoprim (TMP; minimal inhibitory concentration > 4 μg/ml). Synergism between sulfamethoxazole and TMP was present in all strains at a ratio of 1:1. The few clostridia investigated proved more resistant to both compounds. Dihydrofolate reductases from
B. fragilis, C. perfringens
, and some other anaerobic species were isolated. Inhibition profiles with six structurally different inhibitors revealed major differences in all enzymes. For 50% inhibition, the enzyme from
B. fragilis
and all clostridia required concentrations of TMP which were between several hundredfold and 1,000-fold higher than those required for the enzyme of
Escherichia coli
, whereas the enzyme from
Propionibacterium acnes
only needed a threefold higher concentration. In vitro activities of TMP were seen to correspond to the activity at the enzymatic level in
B. fragilis
and
P. acnes
, but correspond to a much lesser extent to the activity at the enzymatic level in clostridia, where a poor penetration is assumed to be involved. Dihydrofolate reductase inhibitors other than TMP were found to be as active as TMP both at the enzyme and in vitro. In
B. fragilis
, higher concentrations of exogenous thymidine were required for increasing the minimal inhibitory concentration of TMP than in
E. coli
and probably also in
C. perfringens
.
Bacitracin Production by Whole Cells Immobilized in Polyacrylamide Gel
Authors: Morikawa Yasushi , Ochiai Keiko , Karube Isao , Suzuki Shuichi
Published: June 2012

Whole cells of
Bacillus
sp., bacitracin-producing bacteria, were immobilized in polyacrylamide gel prepared by using 5% total acrylamide (95% acrylamide monomer and 5%
N
,
N
′-methylenebis acrylamide). Bacitracin production by the immobilized whole cells was examined by using various fermentation media. In starch-bouillon medium, the initial activity of immobilized whole cells for bacitracin production was 20 to 25% that of an equivalent amount of washed cells. With successive utilizations in 1% peptone as reaction medium, activity of the immobilized whole cells increased gradually and reached a steady-state maximum having a value of 80 to 90% of the activity obtained initially with washed cells, whereas the washed cells lost most activity when utilized successively. What appeared to be growth of the bacteria in the gel was observed by electron microscopy. Therefore, the activation of immobilized whole cells during successive utilizations apparently resulted from the growth of whole cells in the gel, especially at the gel surface.
Interpretive Criteria for Cefamandole and Cephalothin Disk Diffusion Susceptibility Tests
Authors: Barry A. L. , Schoenknecht F. D. , Shadomy S. , Sherris J. C. , Thornsberry C. , Washington J. A. , Kammer R. B.
Published: June 2012

A multi-center study of 1,838 clinical isolates established the accuracy of diffusion susceptibility tests with 30-μg cephalothin disks and 30-μg cefamandole disks. The same interpretive zone standards can be applied to tests with either disk but the two drugs cannot be tested interchangeably.
Effects of Carbon Sources on Antibiotic Resistance in
Pseudomonas aeruginosa
Authors: Conrad Robert S. , Wulf R. Gary , Clay Damonda L.
Published: June 2012

The metabolism of branched-chain amino acids, branched-chain acyl derivatives,
d
-glucose,
l
-glutamate, and Mueller-Hinton medium was investigated to determine their effects on the growth, lipid composition, and antibiotic susceptibility of
Pseudomonas aeruginosa
. The unsaturated fatty acid content of the readily extractable lipids was altered by growth on selected branched-chain amino acids and their acyl derivatives. Bacteria grown on branched-chain acyl derivatives became more susceptible to polymyxin B and colistin. The effect acyl derivatives had on increasing susceptibility was also manifest in mixed media which contained both an acyl derivative and a carbon source which did not increase susceptibility. Growth on branched-chain amino acids gave mixed results which were dependent on a number of factors, including unique manifestations of individual amino acids, growth conditions, and availability of other carbon sources. The cultural conditions which altered susceptibility to polymyxin antibiotics did not correlate with similar effects on susceptibility to carbenicillin and gentamicin. An adaptive resistance to polymyxin B was observed when the sole carbon source was
d
-glucose or
l
-glutamate.
Activities of 5,6-Dihydro-5-Azathymidine Against Herpes Simplex Virus Infections in Mice
Authors: Renis Harold E. , Eidson Emerson E.
Published: June 2012

5,6-Dihydro-5-azathymidine (DHAdT), a nucleoside antibiotic inhibitory for herpes simplex virus (HSV) in cell cultures (H. E. Renis, Antimicrob. Agents Chemother.
13:
613–617, 1978), was evaluated in mice with experimental HSV infections. DHAdT protected mice infected with HSV type 1 (HSV-1) when the virus was inoculated intravenously and the drug was given by subcutaneous or oral routes. The activity observed was dependent on the dose and schedule of treatment. Doses of 100 to 400 mg/kg given three to four times daily (at 4-h intervals) for 4 to 5 days gave greater protection than less frequent treatment for shorter time intervals. DHAdT treatment reduced the rate of isolation as well as the HSV-1 titers in homogenates prepared from spinal cords and brains, whereas the titers in kidney homogenates were only marginally affected. The above treatment regime with DHAdT afforded only partial protection to mice infected intracerebrally with HSV-1 or mice inoculated intravaginally with HSV-1 or HSV-2. The antiviral activity of DHAdT was reversed by the co-administration of thymidine. Under these conditions, DHAdT was not toxic in mice.
Purification by Affinity Chromatography and Properties of a β-Lactamase Isolated from
Neisseria gonorrhoeae
Authors: Eriquez Louis A. , D'Amato Richard F.
Published: June 2012

β-Lactamase activity was detected in cell-free preparations obtained from ultrasonic treatment of
Neisseria gonorrhoeae
after growth in liquid medium. Crude preparations of β-lactamase were subjected to affinity chromatography, using several β-lactam antibiotics as ligands bound to agarose supports. Affinity gels produced by coupling 7-aminocephalosporanic acid or 6-aminopenicillanic acid by their amino groups to carboxyl-terminal agarose via a five- to eight-carbon spacer arm proved to be effective chromatography media. β-Lactamase preparations subjected to chromatography using these gels were purified 200-fold, with approximately 80% recovery of active material. Purified preparations were judged homogeneous by their behavior during electrophoresis on polyacrylamide in both the presence and absence of sodium dodecyl sulfate. Characterization of the purified enzyme established a molecular weight of approximately 25,000 and an isoelectric point of 5.4. Analyses of substrate specificity, effect of inhibitors, pH, and kinetic parameters were performed. The evidence suggests that the β-lactamase produced in
N. gonorrhoeae
closely resembles the character of class IIIa (TEM-type) β-lactamases.
Effect of 5-Azacytidine on Cytoplasmic Ribosomal and Messenger Ribonucleic Acids in BSC-1 Cells
Authors: Reuveni Yaffa , Rosenthal Leonard J.
Published: June 2012

5-Azacytidine (5-AzaCR) inhibited the accumulation of 28S and 18S ribonucleic acids (RNAs) in the cytoplasm of treated cells. The inhibition of 28S and 18S RNAs in the cytoplasm of BSC-1 cells was dependent upon the concentration of 5-AzaCR employed and the time of exposure. At a concentration of 200 μg/ml for 2 h, 5-AzaCR inhibited the cytoplasmic 28S and 18S RNAs by 80 and 70%, respectively. The 28S and 18S RNAs that appeared in the cytoplasm of treated cultures had no altered secondary structure, as analyzed by polyacrylamide gel electrophoresis. The inhibitory effect on cytoplasmic 28S and 18S RNAs was found to be reversible, and removal of 5-AzaCR from treated cultures allowed the accumulation of cytoplasmic 28S and 18S RNAs to almost normal levels by 20 h. 5-AzaCR appeared to have no effect upon the synthesis and processing of polyadenylic acid-containing messenger RNA in treated cultures. However, the formation of the 80S ribosomal subunit appeared to be inhibited in drug-treated cells. Moreover, 5-AzaCR treatment caused a disaggregation of polyribosomes and an accumulation of 80S ribosomes.
Effect of Ampicillin and Chloramphenicol Against
Streptococcus pneumoniae
and
Neisseria meningitidis
Authors: Feldman William E. , Zweighaft Teresa
Published: June 2012

Antagonism, determined by isobolograms constructed from data from combinations of ampicillin and chloramphenicol at or below the minimal inhibitory or bactericidal concentrations, was observed against 13 clinical isolates of meningococcus and against one isolate of pneumococcus. Synergy occurred against six strains of pneumococcus and three of meningococcus. Additive effects were noted against 14 isolates of pneumococcus and 5 of meningococcus. There was no relationship between the minimal inhibitory or bactericidal concentrations for the isolates and the occurrence of antagonistic, additive, or synergistic effects. These data indicate that ampicillin and chloramphenicol may be antagonistic in vitro against some strains of pneumococcus or meningococcus.
Cefamandole Therapy in Anaerobic Infections
Authors: Greenberg Richard N. , Scalcini Marcella C. , Sanders Charles V. , Lewis A. Carter
Published: June 2012

Thirty-one adult patients with infections due to anaerobic bacteria were treated with cefamandole.
Bacteroides fragilis
group (17) and
Bacteroides melaninogenicus
(13) were the most frequent anaerobes isolated. Duration of therapy varied from 2 to 49 days. Results were judged satisfactory in 26 cases, and unsatisfactory in 1 case. Four cases could not be evaluated. Adverse reactions occurred in 16 patients and included positive direct Coombs' test without hemolysis, transient liver function abnormalities, phlebitis, reversible neutropenia, fever, eosinophilia, and toxic epidermal necrolysis. The more significant reactions were associated with prolonged therapy. None was lethal. These data suggest that cefamandole is effective in treatment of most anaerobic infections.
Synergistic Effects of Ampicillin-Aminoglycoside Combinations on Group B Streptococci
Authors: Cooper M. D. , Keeney R. E. , Lyons S. F. , Cheatle E. L.
Published: June 2012

The in vitro activity of gentamicin, tobramycin, kanamycin, and amikacin in combination with ampicillin was determined against aminoglycoside-resistant group B streptococci. Synergy in each combination was determined by quantitative kill curves and demonstrated in all the combinations tested.
Killer Phenomenon in Pathogenic Yeast
Authors: Kandel Judith S. , Stern Timothy A.
Published: June 2012

Potentially pathogenic yeast strains from four genera,
Candida, Cryptococcus, Torulopsis
, and
Trichosporon
, were examined for killer activity and sensitivity using
Saccharomyces
and
Torulopsis
strains of known killer status. Tests were performed by using a streak method and by concentration of culture fluid by lyophilization. Of 236 strains examined, killers were found with low prevalence among
Torulopsis
and
Cryptococcus
strains;
Candida
and
Trichosporon
isolates showed no killing activity. Different specificities of killing activity were observed among strains of a single species. Sensitive strains were found with varying frequencies in all genera but
Trichosporon
.
In Vitro System for Studying the Efficacy of Antiviral Agents in Preventing the Reactivation of Latent Herpes Simplex Virus
Authors: Wohlenberg Charles , Openshaw Harry , Notkins Abner L.
Published: June 2012

Antiviral antibody and interferon did not prevent in vitro reactivation of herpes simplex virus in latently infected sensory ganglia. Phosphonoacetic acid and 9-β-
d
-arabinofuranosyladenine blocked reactivation, but this treatment did not eradicate the latent infection.
Comparative Penetration of Various Cephalosporins into Inflammatory Exudate
Authors: Guerrero Isabel C. , MacGregor Rob Roy
Published: June 2012

A rabbit sterile peritonitis model was used to determine the relative penetration of four cephalosporin antibiotics into exudate fluid. Male New Zealand white rabbits were given 120 ml of sterile saline intraperitoneally, and peritonitis developed over the following 8 h, with exudate fluid containing a mean of 17,188 granulocytes per mm
3
at 8 h. Each antibiotic was administered intramuscularly at a dose of 30 mg/kg 3 h after peritonitis was initiated, and serum and peritoneal concentrations were measured 0.5, 1, 2, and 4 h later. Cefamandole gave the highest mean peak serum level (26.8 μg/ml), and cephalothin, cephacetrile, and cephradine all gave peak serum levels between 13 and 15 μg/ml. When peak peritoneal exudate concentration was expressed as a percentage of peak serum concentration, cephradine developed 28.5% of the peak serum level, cephacetrile 27.7%, cephalothin 14.0%, and cefamandole 12.5%. These percentages of exudate penetration were inversely proportional to the degree of serum protein binding: cephradine 26.6%, cephacetrile 36.3%, cephalothin 50%, and cefamandole 88%.
Antimicrobial Susceptibility Testing of
Mycobacterium fortuitum
Complex
Authors: Welch David F. , Kelly Michael T.
Published: June 2012

A total of 24 strains of the
Mycobacterium fortuitum
complex were tested for susceptibility to antimicrobial agents by the disk diffusion and agar dilution techniques. By comparing zones of inhibition obtained with the disk diffusion technique with results of minimal inhibitory concentration determinations, it was shown that disk diffusion results could predict in vitro susceptibility to selected antimicrobial agents. All of 17 strains of
M. fortuitum
were susceptible to ≤1 μg of amikacin per ml. The corresponding average zone of inhibition around a 10-μg amikacin disk was 37 mm. Seven
M. chelonei
strains were more resistant to amikacin, with minimal inhibitory concentrations ranging from 1 to 32 μg/ml, and the corresponding average zone size was 21 mm. Susceptibility of both
M. fortuitum
and
M. chelonei
to tetracycline was variable and none of the
M. chelonei
strains was inhibited by polymyxin B, whereas
M. fortuitum
strains consistently had zones of inhibition around the polymyxin disk. It appears that identification to species of the
M. fortuitum
complex may be of importance with regard to antibiotic susceptibility. Separation of
M. fortuitum
and
M. chelonei
was readily accomplished in the present study by the nitrate reduction and 3-day arylsulfatase tests.
Therapy of Experimental Herpes Simplex Encephalitis with Aciclovir in Mice
Authors: Park No-Hee , Pavan-Langston Deborah , Mclean Sandra L. , Albert Daniel M.
Published: June 2012

This report is concerned with the capacities of aciclovir to protect mice challenged intracerebrally with multiple lethal doses of type 1 herpes simplex virus and to control multiplication of this virus in the brain. With treatment initiated 12 h after inoculation and continued for 4 consecutive days, aciclovir administered subcutaneously in daily doses ranging from 40 to 100 mg/kg led to 21-day survival rates of from 33 to 73% and reduced virus titers by 1 to ½ × 4 logs on postchallenge day 8. The therapeutic accomplishments of the 100-mg/kg doses of aciclovir were comparable to those of 1,000-mg/kg doses of vidarabine (9-β-
d
-arabinofuranosyladenine); however, as measured by impact on body weight, aciclovir was better tolerated than vidarabine at these similarly effective doses.
Inhibition of
Clostridium botulinum
by
p
-Hydroxybenzoic Acid
n
-Alkyl Esters
Authors: Dymicky M. , Huhtanen C. N.
Published: June 2012

Twelve straight-chain esters, C
5
to C
14
, C
16
, and C
18
, of
p
-hydroxybenzoic acid were prepared, and their melting points, solubilities in water at 25°C, infrared spectra, dissociation constants (

pK
a

), and activities against
Clostridium botulinum
were determined. These studies also included four commercial straight-chain esters, C
1
to C
4
. The most potent activity was exhibited by undecyl and dodecyl esters, which are about 300 times as active as sodium nitrite. Quadratic and cubic equations were developed correlating the activity with

pK
a

values and chain length of the esters, respectively.
Significance of Methicillin Tolerance in Experimental Staphylococcal Endocarditis
Authors: Goldman Peggy L. , Petersdorf Robert G.
Published: June 2012

Methicillin-tolerant staphylococci are organisms that are inhibited by low concentrations of the drug but are resistant to its bactericidal effects. The clinical significance of this in vitro phenomenon is unknown. An experimental model of staphylococcal endocarditis in rabbits was used to determine whether methicillin-tolerant staphylococci are particularly difficult to eradicate from infected heart valves. In vitro sensitivity testing was used to identify a tolerant and a nontolerant strain of
Staphylococcus aureus
. Rabbits prepared by the insertion of a polyethylene catheter into the left ventricle and injected with a tolerant strain survived significantly longer than those injected with a nontolerant strain. No significant differences were demonstrated in the prevention of endocarditis with a single prophylactic dose of methicillin, or in the treatment of established endocardial infection with multiple doses of methicillin. In this study, methicillin had the same activity against experimental endocarditis caused by a tolerant and a nontolerant strain of
S. aureus
.
In Vitro Synthesis of Peptidoglycan by β-Lactam-Sensitive and -Resistant Strains of
Neisseria gonorrhoeae
: Effects of β-Lactam and Other Antibiotics
Authors: Brown Christine A. , Perkins Harold R.
Published: June 2012

The synthesis in vitro of peptidoglycan by
Neisseria gonorrhoeae
was studied in organisms made permeable to nucleotide precursors by treatment with ether. Optimum synthesis occurred at 30°C in tris(hydroxymethyl)aminomethane-maleate buffer (0.05 M; pH 6) in the presence of 20 mM Mg
2+
. The incorporation from uridine 5′-diphosphate-
N
-acetyl-[
14
C]glucosamine into peptidoglycan, measured after precipitation of the cells with trichloroacetic acid, was sensitive to the β-lactam antibiotics, bacitracin, diumycin, and tunicamycin and relatively resistant to spectinomycin and tetracycline. Differences in sensitivity between preparations from a β-lactamase producer and a laboratory segregant derived from it were not great. Synthesized peptidoglycan was also fractionated into sodium dodecyl sulfate-soluble and -insoluble portions. β-Lactam antibiotics at concentrations equivalent to the minimal inhibitory concentrations for growth of the organisms did not inhibit peptidoglycan synthesis, but rather caused a small enhancement. At higher concentrations, above about 0.5 μg/ml, incorporation into sodium dodecyl sulfate-insoluble material was progressively inhibited, whereas the amount of sodium dodecyl sulfate-soluble product increased greatly, more than compensating for the loss of the precipitable fraction. Similar observations were made with three strains, and also with the β-lactam clavulanic acid, normally considered as a β-lactamase inhibitor rather than as itself an effective antibiotic.
Rapid, Simple Enzyme Immunoassay for Gentamicin
Authors: Wills P. J. , Wise R.
Published: June 2012

An enzyme immunoassay for gentamicin is described. The assay is accurate and specific and needs only simple equipment.
Ventricular Fluid Levels of Chloramphenicol in Infants
Authors: Yogev Ram , Williams Tommy
Published: June 2012

Investigation of two infants suggested that peak ventricular fluid levels of chloramphenicol after intravenous administration were achieved after 3 h. The penetration of chloramphenicol into ventricular fluid may be unpredictable. In one patient, the peak ventricular fluid level was 57.5% of the peak serum level, and it was only 22.5% in the other patient. This observation may explain some of the past treatment failures when chloramphenicol was utilized in patients with gram-negative ventriculitis and meningitis.
Comparison of the Activities of the New Ureidopenicillins Piperacillin, Mezlocillin, Azlocillin, and Bay k 4999 Against Gram-Negative Organisms
Authors: Verbist Ludo
Published: June 2012

The in vitro activities of the new ureidopenicillins piperacillin, mezlocillin, azlocillin, and Bay k 4999 were compared with those of ampicillin and ticarcillin against 336
Enterobacteriaceae
, 109 nonfermenters, 55
Neisseria
, and 28
Haemophilus influenzae
isolates. Bay k 4999 displayed the largest spectrum of activity and had lower minimal inhibitory concentrations than any of the other penicillins against all of the species tested. Piperacillin showed the same spectrum but was slightly less active than Bay k 4999; it was slightly more effective than mezlocillin against
Enterobacteriaceae
and fully as active as azlocillin against
Pseudomonas
. All ureidopenicillins were substantially more active than ampicillin and ticarcillin. Isolates highly resistant to ampicillin or ticarcillin were also less susceptible to the ureidopenicillins.
Antibacterial Activity of a New 1-Oxa Cephalosporin Compared with That of Other β-Lactam Compounds
Authors: Neu Harold C. , Aswapokee Nalinee , Fu Kwung P. , Aswapokee Prasit
Published: June 2012

The in vitro activity of (6R,7R)-7-{[carboxy(4-hydroxyphenyl)acetyl]amino}-7-methoxy-3-[[(1-methyl -1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-oxa-1-azabicyclo-[4.2.0]oct-2-ene -2-carboxylic acid was tested against isolates of gram-positive and negative bacteria and compared with those of cephalothin, cefuroxime, cefamandole, cefoxitin, cefotaxime, and carbenicillin. The compound was less active than the other compounds when tested against
Staphylococcus aureus
and
Staphylococcus epidermidis
. It had equal or slightly less activity than did cefotaxime when tested against members of the
Enterobacteriaceae
, but was 8- to 32-fold more active than the other cephalosporins against the
Enterobacteriaceae
, inhibiting most isolates at concentrations less than 0.5 μg/ml. The compound was twofold more active than cefotaxime and cefoxitin against
Bacteroides
, and it was twofold more active than cefotaxime and fourfold more active than carbenicillin against
Pseudomonas aeruginosa
. In vitro activity did not correlate with either the presence or type of β-lactamase in either
Enterobacteriaceae
or
Pseudomonas
. The compound showed minimal synergy when combined with aminoglycosides or carbenicillin.
Comparative Activity and β-Lactamase Stability of Cefoperazone, a Piperazine Cephalosporin
Authors: Neu Harold C. , Fu Kwung P. , Aswapokee Nalinee , Aswapokee Prasit , Kung Ket
Published: June 2012

The in vitro activity and β-lactamase stability of 7-[
d
(−)-α-(4-ethyl-2,3-dioxopiperazino-carbonylamino) -
p
-hydroxyphenylacetamido]-3-[(1-methyl)-5-tetrazolylthiomethyl] -Δ
3
-cephem-4-carboxylic acid (cefoperazone), a cephalosporin analog of piperacillin, were compared with the activities and stabilities of other cephalosporins and cephamycins. The compound was less active than cephalothin or cefamandole in inhibiting
Staphylococcus aureus
; it was as active as cefamandole and cefoxitin against most of the
Enterobacteriaceae
but less active than cefotaxime. It was more active than carbenicillin or piperacillin against
Pseudomonas aeruginosa
. In general, the compound was not active against
Bacteroides
. It was hydrolyzed by the β-lactamases of some
Escherichia coli
which hydrolyzed cefamandole, but was stable to most plasmid-mediated, chromosomally mediated, inducible β-lactamases in the
Enterobacteriaceae
and
Pseudomonas
.
Streptomycin Resistance in a Streptomycin-Producing Microorganism
Authors: Piwowarski Janet M. , Shaw Paul D.
Published: June 2012

Cell-free extracts of
Streptomyces bikiniensis
contain an adenosine 5′-triphosphate-dependent kinase which inactivates streptomycin (Sm) and dihydrostreptomycin by phosphorylation. The products have been identified as streptomycin 6-phosphate and dihydrostreptomycin 6-phosphate. Activity was not present in logarithmic-phase cells, which were susceptible to 25 μg of Sm per ml. In stationary-phase cells, activity appeared 12 h before detectable Sm in the medium. These cells were resistant to more than 200 μg of Sm per ml. Certain
S. bikiniensis
isolates selected from cultures treated with acriflavine or ethidium bromide lost the ability to produce Sm and became susceptible to 10 μg of Sm per ml throughout their growth. Cell-free extracts of the dye-treated isolates did not inactivate Sm and lacked streptomycin kinase activity at all stages in development. Ribosomes from resistant cells bound the same amount of [
3
H]dihydrostreptomycin as ribosomes from susceptible cells, and there was no correlation between the uptake of [
3
H]dihydrostreptomycin and resistance. The Sm-inactivating enzyme was identified as streptomycin-6-kinase. These results suggest that phosphorylation by streptomycin-6-kinase is a major factor in resistance in
S. bikiniensis
.
Latent infections of sensory ganglia as influenced by phosphonoformate treatment of herpes simplex virus-induced skin infections in hairless mice
Authors: Klein R J , DeStefano E , Brady E , Friedman-Kien A E
Published: June 2012

Topical treatment with 3% phosphonoformate of herpes simplex virus type 1 (HSV)-induced skin infections of hairless mice reduced the severity of skin lesions when the treatment was initiated 3 h after virus inoculation in the lumbosacral area or 3 and 24 h after inoculation in the orofacial area. The mortality was significantly reduced in lumbosacral-infected mice and was completely prevented in orofacial-infected mice when the treatment was initiated with a delay of 24 h after virus inoculation. However, phosphonoformate did not prevent the establishment of latent herpes simplex virus type 1 infections in the spinal and trigeminal ganglia, even when treatment was initiated as early as 3 h after infection.
Antibiotic activity in vitro against methicillin-resistant Staphylococcus epidermidis and therapy of an experimental infection
Authors: Lowy F D , Walsh J A , Mayers M M , Klein R S , Steigbigel N H
Published: June 2012

Staphylococcus epidermidis is a major pathogen in early prosthetic valve endocarditis and cerebrospinal fluid shunt infections. Approximately 10 to 15% of hospital isolates are methicillin resistant. Ten clinically significant isolates of the latter were collected for antibiotic studies in vitro and in an experimental infection in animals. Time-kill studies of five strains showed gentamicin to be the single most effective antibiotic; however, dwarf colony variants emerged as survivors with two of these strains when challenged with gentamicin alone. The addition of a second antibiotic to gentamicin did not significantly improve the bactericidal rate but prevented the emergence of variant strains. A blood culture isolate of methicillin-resistant S. epidermidis combined with 5% hog gastric mucin was used to establish an experimental intraperitoneal infection in mice. Neither methicillin nor nafcillin treatment reduced mortality below that of untreated animals. Cephalothin treatment delayed early mortality but did not diminish overall mortality. Gentamicin was the most effective single antibiotic, and gentamicin in combination with vancomycin was the most effective regimen overall. The combination of rifampin plus vancomycin was as effective as gentamicin alone. The combinations of cephalothin or nafcillin with gentamicin and cephalothin with vancomycin demonstrated antagonism. The antagonism was not due to multiple injections or drug-drug inactivation.
Piperacillin susceptibility tests by the single-disk agar diffusion technique
Authors: Barry A L , Thornsberry C , Badal R E , Baker C N , Jones R N , Gerlach E H
Published: June 2012

Piperacillin is a new semisynthetic penicillin with a spectrum of activity broader than that of carbenicillin or ticarcillin. Studies were performed to establish standards for agar diffusion susceptibility tests with piperacillin disks. Tests with 100-, 150-, and 200-micrograms piperacillin disks and with 100-micrograms carbenicillin disks were evaluated. With both penicillins, 100-micrograms disks were satisfactory, in spite of the fact that piperacillin is a larger molecule and diffuses at a slower rate. With both carbenicillin and piperacillin disks, resistant strains of Staphylococcus aureus produced zones less than or equal to 28 mm and susceptible strains gave zones greater than or equal to 29 mm in diameter. When testing other microorganisms, zone standards of less than or equal to 13 mm for resistant (minimal inhibitory concentration, greater than or equal to 256 micrograms/ml) and greater than or equal to 17 mm for susceptible (minimal inhibitory concentration, less than or equal to 64 micrograms/ml) are recommended for tests with 100-micrograms piperacillin disks. Similar zone standards are currently recommended for carbenicillin and ticarcillin disk tests.
Beta-lactam resistance in clinical isolates of Escherichia coli caused by elevated production of the ampC-mediated chromosomal beta-lactamase
Authors: Bergström S , Normark S
Published: June 2012

Among cephalothin-resistant isolates from patients with urinary tract infections, six Escherichia coli strains were found to produce elevated amounts of a beta-lactamase indistinguishable from that coded by the ampC gene of E. coli K-12. The resistance levels displayed by these isolates toward a number of beta-lactams were, for five of them, considerably higher as compared with E. coli K-12 with the same amount of beta-lactamase, implying the importance of intrinsic resistance in these isolates. Cefuroxime, and to a lesser extent cefamandole, were stable to hydrolysis by E. coli chromosomal beta-lactamase but acted as inhibitors of the enzyme. Nevertheless, increased beta-lactamase production mediated an increased resistance toward these drugs. No plasmids were found in the isolates, suggesting a chromosomal location for the respective ampC locus.
Alafosfalin, a new inhibitor of cell wall biosynthesis: in vitro activity against urinary isolates in Japan and potentiation with beta-lactams
Authors: Maruyama H B , Arisawa M , Sawada T
Published: June 2012

A new phosphonopeptide, alafosfalin, was evaluated for in vitro antibacterial activity and for synergism with beta-lactams, using 475 Japanese clinical isolates from urinary tract infections. Alafosfalin was found to be highly active against Escherichia coli and moderately active against Serratia, Klebsiella, Enterobacter, and Citrobacter, but less active against gram-positive organisms than were beta-lactams such as cephazolin or ampicillin and inactive against indole-positive Proteus, Pseudomonas, and Acinetobacter. Potentiation with the two beta-lactams (fractional inhibitory concentration less than or equal to 0.5) was found in 10 to 40% of susceptible strains in 4:1 and 1:4 combinations, and to a lesser extent in those species or genera that were insensitive to alafosfalin alone. No cross resistance was seen between alafosfalin and the beta-lactams or any other commonly used antibacterial agents tested. Effect on selected ampicillin-resistant strains, differential sensitivity to alafosfalin among resistant strains of various types, and sensitivity of alafosfalin-insensitive E. coli and Klebsiella to other antibiotics are also discussed.
Antimalarial Properties of Floxacrine, a Dihydroacridinedione Derivative
Authors: Schmidt L. H.
Published: June 2012

Evaluations of the activities of floxacrine [7-chloro-10-hydroxy-3-(4-trifluoromethylphenyl)-3,4-dihydroacridine-1,9(2H, 10H)-dione] in owl monkeys infected with trophozoites of a chloroquine-quinine-resistant strain of
Plasmodium falciparum
, a strain of this plasmodium resistant to both of these quinolines and pyrimethamine, or a strain of
P. vivax
resistant only to pyrimethamine showed that: (i) this compound regularly effected temporary clearance of parasitemia at daily doses of 1.25 to 2.5 mg/kg; (ii) doses required for the cure of established infections were larger by factors of 6 to 64 than those that effected parasite clearance; (iii) there was more than a 10-fold difference in doses required for the cure of infections with the different strains; and (iv) resistance to floxacrine developed rapidly. Evaluations of the activities of floxacrine in rhesus monkeys challenged with sporozoites of
P. cynomolgi
showed that: (i) 0.625-mg/kg doses administered daily throughout the incubation period provided complete protection against infection; (ii) single 40.0-mg/kg doses delivered 2 h before sporozoite challenge were without prophylactic activity; and (iii) daily doses of 40.0 mg/kg, the maximum tolerated level, productive of a hemorrhagic syndrome in some subjects, would not cure established infections. These observations suggest that the potential contribution of floxacrine to malaria therapy would be limited to the prophylactic area and for practical reasons would be restricted there by the requirement for daily dosage.
In vitro antimicrobial inhibition patterns of nutritionally variant streptococci
Authors: Cooksey R C , Swenson J M
Published: June 2012

Twenty-four isolates of nutritionally variant streptococci, previously categorized as species included among the viridans streptococci, were tested for susceptibility to 12 antimicrobial agents. Minimum inhibitory concentrations for these isolates and for a control group of viridans streptococci with no apparent nutritional deficiencies were determined in two microdilution systems. Pyridoxal hydrochloride, which enhances growth of the nutritional variants, was added to one of these microdilution systems but not to the other. An agar dilution method was also used to test the nutritionally variant isolates. Minimum inhibitory concentrations determined by the three methods compared favorably. Penicillin, nafcillin, methicillin, and clindamycin were less effective in vitro against the nutritional variants than were the other antibiotics tested. Streptomycin, however, was less effective against the control isolates.
Susceptibility of Naegleria fowleri to delta 9-tetrahydrocannabinol
Authors: Pringle H L , Bradley S G , Harris L S
Published: June 2012

Growth of the pathogenic amoeboflagellate Naegleria fowleri is inhibited by delta 9-tetrahydrocannabinol (delta 9-THC). delta 9-THC is amoebostatic at 5 to 50 micrograms/ml. delta 9-THC prevents enflagellation and encystment, but does not impair amoeboid movement. Calf serum at 10 and 20% (vol/vol) reduces the antiamoeba activity of delta 9-THC. Only 1-methoxy delta 8-tetrahydrocannabinol, of 17 cannabinoids tested, failed to inhibit growth of N. fowleri. Antinaeglerial activity was not markedly altered by opening the pyran ring, by converting the cyclohexyl ring to an aromatic ring, or by reversing the hydroxyl and pentyl groups on the benzene ring. delta 9-THC prevented the cytopathic effect of N. fowleri on African green monkey (Vero) cells and human epithelioma (HEp-2) cells in culture. delta 9-THC afforded modest protection to mice infected with N. fowleri.
Enhancement of leukocyte activity against Escherichia coli after brief exposure to chloramphenicol
Authors: Pruul H , McDonald P J
Published: June 2012

The effect of brief exposure of Escherichia coli to chloramphenicol on the antibacterial activity of normal human leukocytes was studied by following changes in viability of the bacteria in the presence of leukocytes and serum. Growth was suppressed, and the extent of suppression was directly related to the period of exposure and the concentration of chloramphenicol. When exposed to clinically achievable levels of the drug for 10 min, E. coli failed to resume normal growth for 1 to 4 h in the presence of leukocytes and serum after removal of the drug. The post-antibiotic leukocyte enhancement effect required the presence of antibody and complement. This effect demonstrates the importance of early events in the encounter between antibiotic and microorganism in determining the subsequent activity of host defense components.
Incidence of antibiotic-resistant Escherichia coli associated with frozen chicken carcasses and characterization of conjugative R plasmids derived from such strains
Authors: Caudry S D , Stanisich V A
Published: June 2012

Escherichia coli were isolated at concentrations of about 10(2)/ml from the fluid obtained after thawing each of five frozen chicken carcasses. Between 13 and 89% of the E. coli were resistant to mercury(II) or to at least one of eight antibiotics tested. Multiple resistance was more common than single resistance, and resistances to tetracycline, streptomycin, sulfathiazole, or chloramphenicol were more frequently encountered than was resistance to ampicillin or mercury(II). Resistance to kanamycin, gentamicin, or trimethoprim occurred rarely. Upwards of 30% of the E. coli apparently carried conjugative plasmids and could transfer at least one of their resistance determinants to E. coli K-12. Twenty-five conjugative R plasmids obtained in this way were characterized within strain K-12 by a variety of phenotypic criteria. Twenty could be assigned to the incompatibility groups Inc X, Inc N, Inc FI, or Inc I alpha.
Increased production of beta-lactamase under anaerobic conditions in some strains of Escherichia coli
Authors: Rashtchian A , Nouravarsani R , Miller G R , Gerlach E H
Published: June 2012

A simple biological assay to detect beta-lactamase activity exhibited by selected cultures of Escherichia coli was used to test enzyme production in cells incubated aerobically and anerobically. Anaerobic incubation resulted in increased size of zones of drug inactivation by some beta-lactamase-producing strains. The beta-lactamase activity of cell lysates was determined iodometrically for aerobically and anaerobically grown cells. The specific beta-lactamase activity for anaerobically grown cells was three to five times greater than for aerobically grown cells. Beta-lactamase production was determined to be constitutive in all strains and to be plasmid mediated, as demonstrated by transfer to E. coli K-12 by conjugation.
Pharmacokinetics of intravenous piperacillin in patients undergoing chronic hemodialysis
Authors: Francke E L , Appel G B , Neu H C
Published: June 2012

The pharmacokinetic properties of piperacillin, a piperazine derivative of ampicillin, were determined in seven patients with creatinine clearances less than 7 ml/min who were undergoing chronic, intermittent hemodialysis. A two-compartment linear model was used to analyze the data. Mean elimination half-life was 1.26 +/- 0.1 h; the mean elimination constant was 0.95 +/- 0.08 h-1; the mean volume of distribution was 0.16 +/- 0.02 liters/kg of body weight; the mean volume of the central compartment was 0.10 +/- 0.01 liters/kg of body weight; and the mean clearance was 0.09 +/- 0.01 liters/h per kg of body weight. Mean elimination half-life while off dialysis of 2.1 h.
Phosphorylation of streptozotocin during uptake via the phosphoenolpyruvate: sugar phosphotransferase system in Escherichia coli
Authors: Ammer J , Brennenstuhl M , Schindler P , Höltje J V , Zähner H
Published: June 2012

Mutants of Escherichia coli K-12, Staphylococcus aureus, and Bacillus subtilis defective in the general components (enzyme I, or HPr, or both) of the phosphoenolpyruvate:sugar phosphotransferase system are shown to be resistant to the antibiotic streptozotocin. It is shown here, employing 32P-labeled phosphoenolpyruvate, that wild-type cells of E. coli phosphorylate streptozotocin, whereas with a phosphotransferase system-defective mutant of E. coli the drug is recovered in an unaltered, free form. The internal accumulation of streptozotocin at the steady-state level was about 70 times that of the concentration in the external medium. The antibacterial action of streptozotocin, as well as the uptake of the drug, was inhibited by N-acetyl-D-glucosamine. The uptake of the antibiotic was extremely sensitive to p-chloromercuribenzoate. It is concluded that streptozotocin is taken up by E. coli via the phosphoenolpyruvate:sugar phosphotransferase system and consequently accumulates in the cell at first as streptozotocin-phosphate.
Chlorhexidine as an effective agent against Chlamydia trachomatis in vitro and in vivo
Authors: Nisbet I T , Graham D M , Spicer P E , Tibbs G J
Published: June 2012

In a small field trial, chlorhexidine (50 micrograms/ml) was as effective against clinical trachoma as topical tetracyclines or oral co-trimoxazole; in vitro, 2.5 micrograms/ml was chlamydicidal.
Effect of Isoniazid on the In Vivo Mycolic Acid Synthesis, Cell Growth, and Viability of
Mycobacterium tuberculosis
Authors: Takayama Kuni , Wang Lynn , David Hugo L.
Published: June 2012

When an actively growing culture of the H37Ra strain of
Mycobacterium tuberculosis
was exposed to isoniazid at a concentration of 0.5 μg/ml, the cells began to lose their ability to synthesize mycolic acids immediately. After 60 min, the cells had completely lost this ability. The synthesis of the three mycolate components—α-mycolate, methoxymycolate, and β-mycolate—was inhibited. The viability of the isoniazid-treated cells was unaffected up to about 60 min of exposure, after which time there was a gradual decline in the viability to about 18% after 180 min. Correspondingly, growth of the drug-treated cells slowed down and stopped after 24 hr. The inhibition of the synthesis of mycolic acids was reversible if the drug was removed before the loss of viability set in. Incubation of the viable cells in the absence of the drug for 24 hr restored the mycolate synthesis. These results strongly suggest that the inhibition of the synthesis of the mycolic acids is closely associated with the primary mechanism of action of isoniazid on the tubercle bacilli. The sequence of events which leads to the loss of viability of cells exposed to isoniazid is described.
Butirosin, a New Aminoglycosidic Antibiotic Complex: Antibacterial Activity In Vitro and in Mice
Authors: Heifetz C. L. , Fisher M. W. , Chodubski J. A. , DeCarlo M. O'.
Published: June 2012

Butirosin is a new aminoglycosidic antibiotic complex which has broad gram-negative and gram-positive inhibitory antibacterial activity, as well as some bactericidal properties. Significantly susceptible bacteria include strains of
Staphylococcus aureus
and
Streptococcus pyogenes
, and pathogenic gram-negative species such as
Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis
and
P. vulgaris, Salmonella enteritidis
and
S. typhimurium, Shigella flexneri
and
S. sonnei
. Good activity by parenteral dosing was obtained in various acute mouse infections. Butirosin is especially interesting because of its activity against
Pseudomonas aeruginosa
in vitro, including gentamicin-resistant clinical isolates, and in experimental mouse infections at relatively low doses.
In Vitro Studies of 5-Fluorocytosine Resistance in
Candida albicans
and
Torulopsis glabrata
Authors: Normark Staffan , Schönebeck Jan
Published: June 2012

Spontaneous mutants of
Candida albicans
resistant to 5-fluorocytosine (5-FC) were isolated from a strain susceptible to 5-FC. These mutants were compared with 5-FC-resistant strains of
C. albicans
and
Torulopsis glabrata
isolated from patients treated with the drug and from untreated patients. Resistance to 5-FC was in all cases followed by a decreased susceptibility to 5-fluorouracil. Most strains were also more resistant to 5-fluorouridine and had a lowered incorporation of uridine. In one spontaneous mutant totally resistant to all three 5-fluoropyrimidines, the uridine monophosphate pyrophosphorylase activity was greatly decreased. The 5-FC-resistant strains were of two main phenotypic classes. Class one was unaffected by 5-FC at the highest concentration tested. The growth rate of strains belonging to the other class was markedly decreased by low concentrations of 5-FC, but these strains were still able to form colonies after 7 days of incubation on plates containing very high concentrations of the drug (2,000 μg/ml). The frequency of spontaneous mutation of a susceptible strain to 5-FC resistance was fairly high. The number of mutants growing on media containing 5-FC was unchanged by concentrations ranging from 25 to 500 μg/ml.