bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between Gentamicin Susceptibility Criteria and Therapeutic Serum Levels for
Pseudomonas aeruginosa
in Mouse Infection Model
Authors: Nicas T. I. , Bryan L. E.
Published: June 2012

In this study estimations of in vivo and in vitro gentamicin susceptibility for a series of strains of
Pseudomonas aeruginosa
were compared. The series included an extremely susceptible strain, typically susceptible strains by current susceptibility criteria, and strains with enzymatic and permeability-mediated resistance. In vivo testing was done by using a mice protection test involving six 1-h doses of gentamicin and an inoculum of 50 50% lethal doses of
P. aeruginosa
. Both normal mice and cyclophosphamide-treated mice were used. It was found that peak serum levels and serum levels of gentamicin obtained just prior to the sixth dose (fifth dose trough levels) required for protection were much higher than minimal inhibitory concentrations (MICs) or minimal bactericidal concentrations (MBCs) obtained in high-cation medium. However, first dose trough levels were similar to MICs or MBCs. Only an extremely susceptible strain, 280, could be treated at antibiotic dosages and serum levels which are considered likely to be safe in humans. A distinct inoculum effect was found in the mice tests, with a 10-fold increase in inoculum producing a 4-fold increase in the amount of gentamicin required, but no inoculum effect was found for MICs. These results suggest that current susceptibility criteria in use for gentamicin and
P. aeruginosa
overestimate gentamicin susceptibility, particularly when low-cation growth medium is used for susceptibility testing and when treating disseminated infection.
Potentiation of Antibiotic Bactericidal Activity by Normal Human Serum
Authors: Dutcher B. S. , Reynard A. M. , Beck M. E. , Cunningham R. K.
Published: June 2012

Combinations of certain antibiotics and normal human serum at concentrations at which there was no killing by the agents when used alone were found to be bactericidal for
Escherichia coli
K-12 cells. This effect was observed with tetracycline, streptomycin (SM), trimethoprim, and ampicillin, but not with chloramphenicol or nalidixic acid. Synergy between SM and human serum was also observed against four of nine smooth strains of
E. coli
. A plasmid-bearing strain of
E. coli
K-12 was also killed by combinations of tetracycline or SM plus serum, even though the plasmid conferred resistance to tetracycline and SM. Evidence is presented that the synergy between antibiotics and serum is due to a complement-mediated effect on the bacterial cells that makes the cells more susceptible to the bactericidal effects of the antibiotics.
Evaluation of a Dispensing Instrument (Dynatech MIC-2000) for Preparing Microtiter Antibiotic Plates and Testing Their Potency During Storage
Authors: McMaster Philip R. B. , Robertson E. Arthur , Witebsky Frank G. , MacLowry James D.
Published: June 2012

The MIC-2000 96-channel dispenser was evaluated for accuracy and repeatability of dispensing 50-μl volumes of water. It was found to perform within the manufacturer's specifications for accuracy of ±5%, but not within the limits for repeatability of ±1%. Overall, instrument performance was found to be satisfactory for the antimicrobial susceptibility testing technique which has been implemented in this laboratory. A method is suggested for simple evaluation of the volumes dispensed. A variety of antibiotics may be stored in Trypticase soy broth in Microtiter plates without loss of potency for periods of at least 2 weeks at −20°C and 4 months at −70°C.
Yersinia enterocolitica
: In Vitro Antimicrobial Susceptibility
Authors: Raevuori M. , Harvey S. M. , Pickett M. J. , Martin W. J.
Published: June 2012

Using 21 antimicrobial agents, agar dilution susceptibility tests were carried out against 190 strains of
Yersinia enterocolitica
. Isolates from human, environmental, and animal sources had essentially equal susceptibility patterns.
Antibiotic Biosynthesis by Cofermentation of Blocked Mutants of Two
Micromonospora
Species
Authors: Lee B. K. , Nagabhushan T. L. , Condon R. G. , Cooper A. B. , Waitz J. A.
Published: June 2012

Two aminocyclitol-negative
Micromonospora
mutants representing two different species,
M. purpurea
and
M. inyoensis
, and blocked at different steps in the biosynthetic pathway were paired and cofermented for the synthesis of antibiotics. The two blocked mutants were incapable of producing antibiotics alone except when 2-deoxystreptamine was added. When combined they produced gentamicins A, X
2
, C
1a
, and C
2b
, which all have an amino group at the 2′ position, and gentamicin B, which has a hydroxyl group at this position instead.
Piperacillin: In Vitro Evaluation
Authors: Bodey Gerald P. , Le Blanc Barbara
Published: June 2012

The in vitro activity of a new semisynthetic penicillin, piperacillin, was determined against 577 clinical isolates of gram-positive cocci and gram-negative bacilli. A concentration of 12.5 μg/ml inhibited 92% of isolates of
Pseudomonas aeruginosa
, 82% of
Serratia marcescens
, 73% of
Escherichia coli
, 61% of
Klebsiella
spp., and 42% of
Enterobacter
spp. Most
Proteus
spp. were extremely susceptible; over 85% were inhibited by 0.10 μg/ml. Piperacillin failed to inhibit the growth of gram-negative bacilli when large inocula were used. The type of media and pH had variable effects on the activity of piperacillin, depending upon the organism. Piperacillin was generally less active than PC-904 against gram-negative bacilli, but was consistently more active than carbenicillin and ticarcillin.
Activity of 5-Episisomicin Compared with That of Other Aminoglycosides
Authors: Fu Kwung P. , Neu Harold C.
Published: June 2012

5-Episisomicin, a semisynthetic aminoglycoside, has been shown to inhibit many members of the
Enterobacteriaceae, Pseudomonas aeruginosa
, and
Staphylococcus aureus
. At a concentration of 3.1 μg/ml, more than 90% of
Escherichia coli, Klebsiella pneumoniae, Enterobacter, Citrobacter
, indole-positive
Proteus
, and
Providencia
were inhibited. 5-Episisomicin had activity against
S. aureus, E. coli, Klebsiella, Enterobacter
, and
Citrobacter
similar to gentamicin and netilmicin. It had activity similar to amikacin and netilmicin against many gentamicin-resistant bacteria. The activity of 5-episisomicin was greatest at an alkaline pH and in medium of low magnesium content. Synergy of 5-episisomicin and carbenicillin was found to occur most often against
Pseudomonas
.
UK-18892, a New Aminoglycoside: An In Vitro Study
Authors: Wise R. , Andrews J. M.
Published: June 2012

UK-18892 is a new aminoglycoside antibiotic, a derivative of kanamycin A structurally related to amikacin. It was found to be active against a wide range of pathogenic bacteria, including many gentamicin-resistant strains. The spectrum and degree of activity of UK-18892 were similar to those of amikacin, and differences were relatively minor. UK-18892 was about twice as active as amikacin against gentamicin-susceptible strains of
Pseudomonas aeruginosa
. Both amikacin and UK-18892 were equally active against gentamicin-resistant strains of
P. aeruginosa
. There were no appreciable differences in the activity of UK-18892 and amikacin against
Enterobacteriaceae
and
Staphylococcus aureus
. Cross-resistance between these two antimicrobials was also apparent.
Mode of Incomplete Cross-Resistance Among Pipemidic, Piromidic, and Nalidixic Acids
Authors: Inoue Satoru , Ohue Tomio , Yamagishi Junichi , Nakamura Shinichi , Shimizu Masanao
Published: June 2012

Spontaneous mutants with various patterns of resistance to pipemidic acid (PPA), piromidic acid (PA), and nalidixic acid (NAL) were isolated from
Escherichia coli
K-12. Most mutants were less resistant to PPA than to PA and NAL, and some mutants resistant to PA and NAL were hypersusceptible to PPA. As for the mutants tested, resistance to the drugs was conferred by mutations at
nalA
and new
nal
genes designated as
nalC
and
nalD
, both of which were located at about 82 min on the recalibrated map. Resistance to PA and NAL was due to decreased sensitivity of the bacterial DNA synthesizing system to them and insufficient drug transport, whereas resistance to PPA was only due to the former.
Erythropoietin Concentration in Amphotericin B-Induced Anemia
Authors: MacGregor Rob R. , Bennett John E. , Erslev Allan J.
Published: June 2012

Amphotericin B was given to six patients with systemic fungal infections. A dose averaging 1.78 g, administered from 42 to 144 days, was associated with a fall in hematocrit to a mean value of 25.8%. Despite this degree of anemia, no elevation of erythropoietin concentrations in urine or serum could be detected. Thus, amphotericin appears to cause anemia by inhibiting erythropoietin production rather than by suppressing bone marrow activity directly.
In Vitro Comparison of Kanamycin, Kanendomycin, Gentamicin, Amikacin, Sisomicin, and Dibekacin Against 200 Strains of
Pseudomonas aeruginosa
Authors: Paradelis A. G. , Douboyas J. , Stathopoulos G. , Grigoriadou-Edipides A. , Triantaphylidis C. , Papapanagiotou J.
Published: June 2012

The antimicrobial activity of kanamycin, kanendomycin, gentamicin, amikacin, sisomicin, and dibekacin against 200 strains of
Pseudomonas aeruginosa
was compared. Dibekacin was found to be the most active against the tested organisms, whereas the other aminoglycoside antibiotics fell in the following order of diminishing antibacterial potency: amikacin, sisomicin, gentamicin, kanendomycin, and kanamycin. Seven strains showed high-level resistance to gentamicin (minimal inhibitory concentration, 400 μg/ml), and two of them were also resistant to amikacin and sisomicin (minimal inhibitory concentration, 75 μg/ml). The minimal inhibitory concentration of dibekacin for these seven strains was 0.625 μg/ml.
Comparative Susceptibilities of Anaerobic Bacteria to Metronidazole, Ornidazole, and SC-28538
Authors: Goldstein Ellie J. C. , Sutter Vera L. , Finegold Sydney M.
Published: June 2012

The susceptibilities of 284 anaerobic bacteria, including 55 strains of the
Bacteroides fragilis
group, were determined by an agar dilution technique to metronidazole and two newer nitroimidazoles, ornidazole and SC-28538. All three agents showed marked in vitro activity against virtually all anaerobic bacteria tested. At concentrations ≤1 μg/ml, SC-28538 was significantly more active than either metronidazole or ornidazole. At concentrations of >1 μg/ml, the activities of all three agents were comparable.
Propionibacterium
and
Actinomyces
showed significant resistance to all three agents. Anaerobic and microaerophilic members of the genus
Streptococcus
were also often resistant, in contrast to
Peptococcus
and
Peptostreptococcus
strains. In addition, the bactericidal activities of ornidazole and SC-28538 were determined against 27 strains of the
B. fragilis
group by a broth dilution technique. The minimal inhibitory and minimal bactericidal concentrations of each agent were very close. At concentrations of ≤0.5 μg/ml, SC-28538 showed greater bactericidal activity; at concentrations of ≥2 μg/ml, the activies of both agents were similar.
Generation of Superoxide Anions and Hydrogen Peroxide from β-Lapachone in Bacteria
Authors: Cruz Fernando S. , Docampo Roberto , Boveris Alberto
Published: June 2012

β-Lapachone markedly increased the generation of superoxide anions and hydrogen peroxide by subcellular membranes of
Bacillus subtilis
and
Bacillus stearothermophilus
. Peroxide generation by β-lapachone was parallel to the inhibition of growth in both microorganisms.
Susceptibility of 40 Lactobacilli to Six Antimicrobial Agents with Broad Gram-Positive Anaerobic Spectra
Authors: Bayer Arnold S. , Chow Anthony W. , Concepcion Nelydia , Guze Lucien B.
Published: June 2012

The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of 40 lactobacillus strains were determined against six antibiotics with broad anaerobic spectra. Penicillin, ampicillin, clindamycin, and cephalothin were the most active inhibitory agents, with 95 to 100% of the strains inhibited at clinically achievable serum levels. However, despite the inhibitory efficacy of these four agents, only 5 to 22% of the isolates were killed at achievable concentrations. MBC:MIC ratios were high, ranging from 30:1 for cephalothin to 266:1 for ampicillin. Cefoxitin and metronidazole were generally ineffective against lactobacilli, with 87.5 to 100% of strains having unachievable MICs and/or MBCs. These findings may partially explain the clinical observations noting the inability to eradicate endocarditic lactobacillemias despite readily achievable MICs.
Penetration of Methicillin, Oxacillin, and Cephalothin into Bone and Synovial Tissues
Authors: Fitzgerald Robert H. , Kelly Patrick J. , Snyder Robert J. , Washington John A.
Published: June 2012

The penetrations of methicillin, oxacillin, and cephalothin into cortical bone and synovial tissues were studied 1 h after their intravenous administration in 105 patients having arthroplasty of the hip. Although the lowest serum levels were noted with cephalothin (
P
< 0.01), more patients receiving cephalothin achieved osseous drug levels inhibitory to staphylococci (
P
< 0.01). Differences in the penetration of the three agents into synovial tissues were not statistically significant.
Effect of Antibiotics on the Prevention of Experimental
Bacteroides fragilis
Endocarditis
Authors: Goldman Peggy L. , Durack David T. , Petersdorf Robert G.
Published: June 2012

The relative efficacy of single doses of antibiotics in modifying the development of
Bacteroides fragilis
subsp.
fragilis
endocarditis was studied in an experimental model. Antibiotics were administered 0.5 h before intravenous injection of
B. fragilis
subsp.
fragilis
into rabbits prepared by insertion of a polyethylene catheter into the left side of the heart; 48 h later, intracardiac vegetations were excised and cultured anaerobically.
B. fragilis
was recovered from 92% of untreated animals. After a single dose of procaine penicillin G (250 mg/kg intramuscularly), 80% of the animals remained infected. Chloramphenicol (30 mg/kg), carbenicillin (50 mg/kg), and metronidazole (10 mg/kg) were also ineffective (76, 80, and 75% infected, respectively). Cefamandole (30 mg/kg), cefoxitin (30 mg/kg), and erythromycin (30 mg/kg) were significantly more active (50, 55, and 45% infected, respectively), as were higher doses of carbenicillin. Clindamycin (50 mg/kg) was the most effective regimen (11% infected). At present, the relevance of these results to the therapy of serious
B. fragilis
infections is not known, but this model may prove useful in the evaluation of the prevention of
B. fragilis
subsp.
fragilis
bacteremia.
Activity of Derivatives and Analogs of Dapsone Against
Mycobacterium leprae
Authors: Levy Louis
Published: June 2012

Of 25 dapsone derivatives and analogs screened for activity against
Mycobacterium leprae
in the mouse footpad system, only 7 were active. All seven were metabolized to or contaminated with dapsone.
Comparative Study of Ten Bacteriocins of
Clostridium perfringens
Authors: Mahony D. E. , Li A.
Published: June 2012

Bacteriocins of
Clostridium perfringens
were prepared by ammonium sulfate precipitation of supernatant broth from 10 bacteriocinogenic strains. These bacteriocins were compared with respect to their ability to produce spheroplasts in a sensitive indicator strain; their inducibility; sensitivity to pH, proteolytic enzymes, and boiling; and their effect on macromolecular synthesis. Two bacteriocins were stable over a wide range of pH values and resisted boiling, and three bacteriocins were resistant to trypsin. Five bacteriocins shut down DNA, RNA, and protein synthesis; three bacteriocins had varying effects on DNA and RNA synthesis; and two bacteriocins had little effect on macromolecular synthesis. Antiserum prepared against one bacteriocin highly neutralized three bacteriocins with partial neutralization of five others; two bacteriocins were unaffected. Mutant strains selected for resistance to bacteriocin 28 also demonstrated coresistance to two other closely related bacteriocins and partial resistance to five others.
Simple Sensitive Microbioassay for Adenine Arabinoside and Hypoxanthine Arabinoside in Human Plasma
Authors: Bryson Yvonne J. , Sweetman Lawrence , Connor James D.
Published: June 2012

Previous methods using low- or high-pressure liquid chromatography and UV absorbance for quantitation of arabinosides in plasma can practically detect only ≥200 ng of adenine arabinoside and ≥100 ng of hypoxanthine arabinoside per ml, and they require expensive equipment and expert technical assistance. We describe in this report a simple quantitative microbioassay for arabinosides in human plasma based on their ability to inhibit the cytopathic effect of vaccinia virus in an adenosine deaminase-free cell culture system. Using prior separation of nucleosides in plasma by thin-layer chromatography, followed by the microbioassay, we quantitated adenine arabinoside with a sensitivity of ∼4 ng/ml and hypoxanthine arabinoside at ∼625 ng/ml. This assay method is simple, sensitive, and reproducible, requires small plasma samples, measures biological activity, and is adaptable to routine use. It is an important tool for evaluating the pharmacology of adenine arabinoside and Ara-AMP in patients in current clinical trials.
Effect of Protein Binding on the Activity of Penicillins in Combination with Gentamicin Against Enterococci
Authors: Glew Richard H. , Moellering Robert C.
Published: June 2012

To assess the effect of protein binding by human serum on the synergistic interaction of penicillins with gentamicin, time-kill curves were determined for four penicillins alone and in combination with gentamicin against 10 blood isolates of enterococci. Killing curves demonstrated synergism with penicillin G plus gentamicin against all 10 strains in either broth or 50% human serum. In broth the combinations of nafcillin plus gentamicin and oxacillin plus gentamicin were synergistic against 10 of 10 strains and 4 of 10 strains, respectively. However, in serum, nafcillin plus gentamicin was synergistically bactericidal against only two strains and oxacillin plus gentamicin against none. Methicillin plus gentamicin was synergistic against none of the enterococci in either medium. Thus, the semisynthetic, penicillinase-resistant penicillins are unlikely to be effective in the therapy of patients with enterococcal endocarditis.
Influence of Suspending Media upon the Susceptibility of
Pseudomonas aeruginosa
NCTC 6750 and Its Spheroplasts to Polymyxin B
Authors: Klemperer Ruth M. , Gilbert P. , Meier Anna M. , Cozens R. M. , Brown M. R. W.
Published: June 2012

The lytic and bactericidal actions of polymyxin B on whole cells and spheroplasts of
Pseudomonas aeruginosa
varied markedly with the suspending media, and there was little correlation between them. Relative rates of lysis of these preparations and also of
Bacillus megaterium
protoplasts suggested that polymyxin causes progressive damage to the cytoplasmic membrane, such that membrane permeability towards various ions increased as follows: K
+
> Na
+
> NO
3
−
> Cl
−
, Ca
2+
, H
2
PO
4
−
/HPO
4
2−
. Impermeant compounds, such as NaCl and sucrose, protected whole cells against lysis but not against death. It is suggested that lysis of whole cells by polymyxin is a secondary effect, resulting from entry of solutes normally excluded by the cytoplasmic membrane and the fragility of the damaged outer membrane. Because the degree of lysis varies with the external solutes, it should be treated with caution as a descriptor of polymyxin activity.
Aminoglycoside-Modifying Enzymes Among Clinical Isolates of
Acinetobacter calcoaceticus
subsp.
anitratus
(
Herellea vaginicola
): Explanation for High-Level Aminoglycoside Resistance
Authors: Murray Barbara E. , Moellering Robert C.
Published: June 2012

Acinetobacter calcoaceticus
subsp.
anitratus
(
Herellea vaginicola
) is an important cause of nosocomial infection in our hospital where
A. calcoaceticus
subsp.
anitratus
is the most frequently isolated gram-negative species resistant to one or more of the aminoglycoside antibiotics. Of 167 strains tested for susceptibility to aminoglycosides, only 6 strains were found that were resistant to ≥128 μg of kanamycin per ml; all others were susceptible to ≤32 μg/ml. Five of these six strains were found to produce aminoglycoside-modifying enzymes. Two strains produced a phosphotransferase which mediates resistance to kanamycin and neomycin; three strains produced an acetyltransferase which mediates resistance to kanamycin, tobramycin, and amikacin (minimal inhibitory concentration ≥ 128 μg/ml for each drug). No strain with lower level resistance to kanamycin, tobramycin, or amikacin had enzyme activity. Fourteen strains resistant to gentamicin failed to show significant enzymatic modification of that antibiotic. Although agarose gel electrophoresis of deoxyribonucleic acid preparations from the enzyme-producing strains showed plasmid bands in all, no transfer of aminoglycoside resistance could be achieved, nor was it cured by exposure to novobiocin, ethidium bromide, acridine orange, heat, or prolonged storage. Resistance to mercuric chloride, present in 2 of 60 strains, was lost by 1 strain after exposure to novobiocin, and the loss of resistance was associated with an apparent deletion of plasmid deoxyribonucleic acid.
Growth Conditions and Rifampin Susceptibility
Authors: Koch Arthur L. , Gross Gayle H.
Published: June 2012

The susceptibility of
Escherichia coli
to rifampin was measured during unlimited growth in rich and poor media and during chemostat growth limited by the carbon source. During batch growth at low turbidities, the susceptibility of the bacteria increased as the growth rate decreased, consistent with the longer time available for drug penetration in the poorer media. During chemostat culture, the bacteria remained highly susceptible or became genetically resistant, dependent on the manner in which the bacteria were exposed to the antibiotic. If the concentration of rifampin was abruptly raised, susceptible cells were replaced by genetically resistant cells. However, if the concentration of antibiotic was raised slowly, the genetically susceptible cells continued to grow. This difference in response of chemostat cultures according to mode of drug administration was attributed to an inducible detoxification of the drug by the bacteria, because the susceptible genotype is maintained only when the concentration of rifampin is increased gradually and when a high population of cells is maintained. Direct evidence for the inactivation of the rifampin from the bioassay of culture supernatants is presented.
Radiometric Method for Determining the Susceptibility of Yeasts to 5-Fluorocytosine
Authors: Hopfer Roy L. , Mills Karen , Gröschel Dieter
Published: June 2012

A rapid method for determining the susceptibility of yeasts to 5-fluorocytosine by using the Bactec radiometric system is described.
Dihydrofolate Reductase from
Neisseria
sp
Authors: Averett Devron R. , Roth Barbara , Burchall James J. , Baccanari David P.
Published: June 2012

Members of the genus
Neisseria
are relatively nonsusceptible to trimethoprim, an inhibitor of dihydrofolate reductase. For example, the minimal inhibitory concentration (MIC) of trimethoprim for
N. gonorrhoeae
ranges from 2 to 70 μg/ml, whereas the MIC for
Escherichia coli
is 0.2 μg/ml or less. In an effort to understand this difference, dihydrofolate reductase was partially purified from five
Neisseria
species and compared with the enzyme from
E. coli. N. gonorrhoeae
dihydrofolate reductase was similar to that from
E. coli
in molecular weight (18,000) and affinity for the substrates reduced nicotinamide adenine dinucleotide phosphate and dihydrofolate (

K
m

= 13 and 8 μM, respectively). However, the gonococcal enzyme had a decreased affinity for trimethoprim, with an apparent

K
i

of 45 × 10
−9
M, some 30-fold greater than the
E. coli
value of 1.2 × 10
−9
M. These enzymes also differed in their isoelectric points and pH activity profiles. Within the genus
Neisseria
, the dihydrofolate reductase isolated from
N. meningitidis
and
N. lactamica
resembled the
N. gonorrhoeae
enzyme, and only small differences were detected for the
N. flavescens
and
Branhamella catarrhalis
dihydrofolate reductases. These data indicate that the relatively poor affinity of trimethoprim for the dihydrofolate reductase from these organisms may be largely responsible for the relative nonsusceptibility of
Neisseria
sp. to trimethoprim. The contribution of other resistance mechanisms to the overall nonsusceptibility was assessed. Strains of
N. gonorrhoeae
with altered cell envelope permeability had MIC values less than twofold different from those of isogenic wild-type strains. Also, a direct relationship was observed between the affinity of trimethoprim analogs for gonococcal dihydrofolate reductase and the MIC of these compounds for the gonococcus. These observations suggest that the cell envelope of
N. gonorrhoeae
is not impermeable to trimethoprim. Changes in the amount of dihydrofolate reductase activity could cause alterations in the susceptibility of the gonococcus to trimethoprim, as demonstrated with
N. gonorrhoeae
strains selected for trimethoprim resistance after chemical mutagenesis. However, the level of dihydrofolate reductase activity in wild-type
N. gonorrhoeae
was similar to that of
E. coli
, indicating that the difference in the susceptibility of these organisms is not due to greater amounts of enzyme in
N. gonorrhoeae
.
Effect of a
Salmonella
Group H1 R Factor on Virulence and Response of Infections to Antimicrobial Therapy
Authors: Butler Thomas , Shuster C. W. , Franco Amalia
Published: June 2012

A group H1 R factor encoding resistance to chloramphenicol, streptomycin, sulfonamide, and tetracycline was transferred into
Salmonella typhimurium
LT-2. The virulence of LT-2 for mice, as assessed by intraperitoneal 50% lethal dose and the number of organisms in the spleen, was not affected by the R factor. On the other hand, the R factor conferred resistance in mouse infections to therapy with chloramphenicol and trimethoprim plus sulfamethoxazole.
Antimicrobial Susceptibilities of Rough, Smooth, and Mucoid Colony Types of
Pseudomonas
Isolated from Cystic Fibrosis Patients
Authors: Maybury Bonnie A. , Blessing-Moore Joann , deWit Sharon A. , Lewiston N. J. , Yeager Anne S.
Published: June 2012

Minimal inhibitory concentrations of carbenicillin, chloramphenicol, tetracycline, gentamicin, tobramycin, and trimethoprim–sulfamethoxazole were determined for rough, smooth, and mucoid
Pseudomonas
sp. isolates from sputa collected from 40 cystic fibrosis patients. Ninety-four percent of the minimal inhibitory concentrations obtained by using mixed inocula of colonies of different morphological types fell within one serial dilution of the most resistant minimal inhibitory concentration obtained when each colony type was tested separately.
Peptidoglycan Transpeptidase Inhibition in
Pseudomonas aeruginosa
and
Escherichia coli
by Penicillins and Cephalosporins
Authors: Moore Brian A. , Jevons Sidney , Brammer Keith W.
Published: June 2012

Peptidoglycan transpeptidase activity has been studied in cells of
Escherichia coli
146 and
Pseudomonas aeruginosa
56 made permeable to exogenous, nucleotide-sugar peptidoglycan precursors by ether treatment. Transpeptidase activity was inhibited, in both organisms, by a range of penicillins and cephalosporins, the
Pseudomonas
enzyme being more sensitive to inhibition in each case. Conversely, growth of
E. coli
146 was more susceptible to these antibiotics than growth of
P. aeruginosa
56. Furthermore, similar transpeptidase inhibition values were ob-obtained for the four penicillins examined against the
Pseudomonas
enzyme, although only two of these (carbenicillin and pirbenicillin) inhibited the growth of this organism. We therefore conclude that the high resistance of
P. aeruginosa
56 to growth inhibition by most β-lactam antibiotics cannot be due to an insensitive peptidoglycan transpeptidase.
Antibiotic Susceptibility of
Neisseria gonorrhoeae
Strains from Europe and Africa
Authors: Piot Peter , Van Dyck Eddy , Colaert Jan , Ursi Jean-Paul , Bosmans Eugène , Meheus André
Published: June 2012

The in vitro activities of 16 antimicrobial agents were tested by a plate dilution method against 268 unselected isolates of
Neisseria gonorrhoeae
from Belgium, Rwanda, Swaziland, and Zaire. Fifteen β-lactamase-producing strains isolated in Europe from various origins were also tested. There were significant regional variations in antimicrobial agent susceptibility, even among the African isolates, with the Rwandan and Zairean strains being most resistant. Benzylpenicillin and ampicillin were equally active in all but the β-lactamase-producing strains. Among the cephalosporins, cefotaxime was by far the most active, followed by cefuroxime, cefamandole, cefoxitin, and cefaclor, in that order. All strains were susceptible to spectinomycin, thiamphenicol, kanamycin, and rifampin, with the exception of one highly rifampin-resistant isolate and a moderately thiamphenicol-resistant strain. Twenty-six percent of the isolates were highly resistant to streptomycin. Six percent of the gonococci had a minimal inhibitory concentration for tetracycline greater than 2 μg/ml. Clavulanic acid inhibited the β-lactamase activity of the gonococci tested and improved markedly the activities of ampicillin and amoxicillin against β-lactamase-producing strains.
Effect of Pyran on Latency After Herpes Simplex Virus Infections
Authors: Morahan Page S. , Cline Paul F. , Breinig Mary C. , Murray Byron K.
Published: June 2012

The immunomodulator pyran protected mice against both herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections. In infections of the lip with HSV-1, prophylactic administration of pyran reduced the severity of the herpetic lesions and enhanced their resolution, but did not decrease the high incidence of development of latent HSV-1 infection of the trigeminal ganglia. In vaginal infections with HSV-2, prophylactic administration of pyran either systemically or locally reduced mortality, reduced the incidence of mice with vaginal HSV-2 infection, and did not alter the low incidence of latent infection of the spinal dorsal root ganglia. Pyran treatment before systemic herpetic infection after intravenous inoculation of HSV-2 also reduced mortality and virus replication, as evidenced by a decreased antibody response in the survivors, and it either reduced latent infection in the spinal dorsal root ganglia or did not predispose mice to latent infection. Treatment with the immunomodulator appeared to inhibit or reduce HSV infection early in viral pathogenesis in all three model systems, producing protection from clinical disease and resulting in less virus to induce a systemic antibody response, with either a reduction in latent virus infection or no enhancement of development of latency. In all of the HSV models, the development of latent herpetic infection was closely correlated with sufficient virus replication early in the infection to induce a systemic neutralizing-antibody response.
Comparison Between Agar and Broth Minimum Inhibitory Concentrations of Cefamandole, Cefoxitin, and Cefuroxime
Authors: Rylander Margareta , Brorson John-Erik , Johnsson Jan , Norrby Ragnar
Published: June 2012

The in vitro susceptibility to cefamandole, cefoxitin, and cefuroxime of clinical isolates of
Streptococcus faecalis, Klebsiella
, and indole-positive
Proteus
was assayed using minimum inhibitory concentration (MIC) determinations in broth and on solid media. It could be demonstrated that the agar dilution MICs obtained when
S. faecalis
was tested against cefuroxime and when indole-positive
Proteus
strains were tested against cefamandole tended to be considerably lower than those obtained with the broth dilution technique. The
Klebsiella
strains tested did not show any major differences with regard to MICs in broth or on solid media. Using an animal experimental infection model it could be demonstrated that with indole-positive
Proteus
the higher broth MIC correlated better to the observed data than the lower agar MIC when a β-lactamase-producing strain was tested. The data obtained indicated that the β-lactamase of the indole-positive
Proteus
strain was inducible. The results of the study gave evidence for a risk of false susceptibility of some bacterial species against cefamandole when agar techniques, e.g. paper disk diffusion, are used. For cefuroxime, the same phenomenon can be expected with
S. faecalis
and to some extent with indole-positive
Proteus
. In this study, cefoxitin seemed considerably less affected by the technique used for susceptibility testing.
Effect of Time and Concentration Upon Interaction Between Gentamicin, Tobramycin, Netilmicin, or Amikacin and Carbenicillin or Ticarcillin
Authors: Pickering Larry K. , Gearhart Pam
Published: June 2012

An aminoglycoside antibiotic and carbenicillin or ticarcillin are widely used in the treatment of patients with gram-negative bacillus infections. This study evaluated the effect of time upon in vitro interaction between mixtures of four aminoglycosides at two concentrations with carbenicillin or ticarcillin at four concentrations. By linear regression analysis, the inactivation of each aminoglycoside was shown to be directly proportional to the concentration of carbenicillin (
P
< 0.001). Inactivation was significantly (
P
< 0.01) greater for gentamicin and tobramycin than for amikacin or netilmicin at all carbenicillin concentrations. At carbenicillin concentrations of 300 and 600 μg/ml, significantly (
P
< 0.005) less inactivation of amikacin occurred when compared to netilmicin. Ticarcillin produced a significant (
P
< 0.025) inactivation of gentamicin and tobramycin, with inactivation being directly proportional to ticarcillin concentration. No inactivation of amikacin or netilmicin activity occurred unless the ticarcillin concentration was 600 μg/ml. No significant change in aminoglycoside activity occurred when stored with ticarcillin or carbenicillin at concentrations ranging from 100 to 600 μg/ml at −70°C for 56 days. When an aminoglycoside and carbenicillin or ticarcillin are indicated in patients with renal failure, this study supports the use of ticarcillin with either amikacin or netilmicin.
Phosphonopeptides as Antibacterial Agents: Rationale, Chemistry, and Structure-Activity Relationships
Authors: Atherton Frank R. , Hali Michael J. , Hassall Cedric H. , Lambert Robert W. , Ringrose Peter S.
Published: June 2012

Peptide mimetics with C-terminal residues simulating natural amino acids have been designed as inhibitors of bacterial cell wall biosynthesis. The phosphonopeptide series consisting of various
l
and
d
residues of natural amino acids combined with 1-aminoalkyl (and aryl-alkyl-) phosphonic acid residues had the most interesting antibacterial properties when the C-terminal residue was
l
-1-aminoethylphosphonic acid. The in vitro antibacterial activities of representative phosphonodi- to phosphonohexapeptides were investigated. The antibacterial action of the active compounds has been explained in terms of transport into the bacterial cell and intracellular release of the alanine mimetic, which interferes with the biosynthesis of the peptidoglycan of the bacterial cell wall.
Clinical and Laboratory Evaluation of Cefamandole in the Therapy of
Haemophilus
spp. Bronchopulmonary Infections
Authors: Delgado Dennis G. , Brau Carmen J. , Cobbs C. Glenn , Dismukes William E.
Published: June 2012

A prospective, randomized, single-blind comparison of parenteral cefamandole and ampicillin was conducted in 27 hospitalized adult patients with pneumonia or purulent tracheobronchitis due to
Haemophilus
spp. Patients received either parenteral cefamandole or ampicillin in a dose of 1 g every 6 h. Cefamandole was as effective and safe as ampicillin. Of the 14 patients treated with cefamandole, 13 were considered cured, as were 12 of the 13 treated with ampicillin. One patient in each treatment group improved clinically but did not clear his sputum of
Haemophilus
spp. One patient treated with cefamandole had a recurrence of
Haemophilus
spp. bronchitis 9 days after cure. Adverse effects were more common in the cefamandole-treated group (50% versus 15%), but were mild and did not require discontinuation of therapy in any patient. The in vitro susceptibilities of 64 clinical isolates of
Haemophilus
spp. to 10 antibiotics were determined. Cefamandole was the most active of the cephalosporin-cephamycin antibiotics tested, inhibiting 98% of 61 non–beta–lactamase–producing isolates at 2 μg/ml and 100% at 4 μg/ml. Cefamandole inhibited the three ampicillin-resistant isolates at 2 μg/ml or less. Cephapirin, cefoxitin, and cephalothin were the next most active, whereas cefazolin and cephradine were the least active.
Comparative Pharmacokinetics of Cephalexin, Cefaclor, Cefadroxil, and CGP 9000
Authors: Lode Hartmut , Stahlmann Ralf , Koeppe Peter
Published: June 2012

In a randomized crossover study, the pharmacokinetics of three new cephalosporin antibiotics, cefaclor, cefadroxil, and CGP 9000, in comparison to cephalexin, were determined after oral administration, by capsules, of 1,000 mg on an empty stomach in 12 normal subjects. Serum concentrations were measured during a period of 8 h, and urine recovery was measured during 24 h. The significant parameters of bioavailability of an orally administered substance were determined. The maximal serum concentrations (

y
max

) for cephalexin, cefaclor, cefadroxil, and CGP 9000 (in milligrams per liter) were: 38.8 ± 8.1; 34.6 ± 7.8; 33.0 ± 5.4; and 23.3 ± 7.3, respectively. The areas under the curve (in hours × milligrams per liter) were: 93.0 ± 14.8; 74.5 ± 9.9; 70.1 ± 9.0; and 108.5 ± 18.4, respectively. In a further crossover study with six subjects, 1,000 mg of cephalexin and of cefadroxil were given during a standard breakfast. The

y
max

of cephalexin decreased to 23.1 ± 6.6 mg/liter, in contrast to cefadroxil, with an unchanged

y
max

of 32.7 ± 3.4 mg/liter.
In Vitro Comparison of Rosamicin and Erythromycin Against Urinary Tract Pathogens
Authors: Eickhoff Theodore C. , Ehret Josephine M.
Published: June 2012

The in vitro activity of rosamicin and erythromycin was compared at various pH values against 311 strains of bacteria representing common urinary tract pathogens. Alkalinization of the media consistently and significantly increased the antibacterial activity of rosamicin against all of the organisms tested. This was also true for erythromycin except when tested against strains of
Proteus
. At pH 8, rosamicin was two- to sixfold more active than erythromycin against
Enterobacteriaceae
. The activity of both antibiotics against
Pseudomonas aeruginosa
was very similar when tested at pH 8. Erythromycin was twice as active as rosamicin at pH 8 against group D streptococci. The activity of both antibiotics was bacteriostatic and inoculum size dependent, regardless of the organism tested or the pH of the test media. The greater activity of rosamicin against
Enterobacteriaceae
warrants clinical investigation.
In Vitro Activity of Sodium Fusidate Against Anaerobic Bacteria
Authors: Steinkraus G. E. , McCarthy L. R.
Published: June 2012

The microtiter broth dilution method was employed to determine the in vitro susceptibility of 525 recent clinical isolates of anaerobic bacteria to sodium fusidate. The minimal inhibitory concentrations of sodium fusidate ranged from ≤0.06 to 1.0 μg/ml for 155 strains of anaerobic gram-positive rods and 130 strains of anaerobic gram-positive cocci. Minimal inhibitory concentrations ranging from ≤0.06 to 32 μg/ml were observed for 240 strains of anaerobic gram-negative rods. Among the latter group a minimal inhibitory concentration of 16 μg/ml or greater was encountered with 16% of 45
Bacteroides fragilis
strains, 19% of 32
Bacteroides thetaiotaomicron
, and all 7 strains of
Fusobacterium necrophorum
. Minimal inhibitory concentrations for
Veillonella parvula
, the only gram-negative coccus tested, ranged from 0.5 to 8.0 μg/ml.
Antimicrobial Susceptibility Testing of Pneumococci: Determination of Kirby-Bauer Breakpoints for Penicillin G, Erythromycin, Clindamycin, Tetracycline, Chloramphenicol, and Rifampin
Authors: Jacobs M. R. , Mithal Y. , Robins-Browne R. M. , Gaspar M. N. , Koornhof H. J.
Published: June 2012

Antimicrobial susceptibility testing of pneumococci is now essential to monitor for the presence of resistance to agents such as the penicillins, macrolides, lincomycins, chloramphenicol, and tetracycline. In this study, clinical isolates of a selection of resistant South African strains were tested for antimicrobial susceptibility by minimal inhibitory concentration (MIC) determination and by a modified Kirby-Bauer disk diffusion technique, using Mueller-Hinton medium supplemented with 5% horse blood. Disk diffusion breakpoints were determined for penicillin G, erythromycin, clindamycin, tetracycline, chloramphenicol, and rifampin. Reliable results were obtained on disk diffusion for all these agents except for penicillin G. With 6-μg penicillin G disks, zones of strains with intermediate penicillin susceptibility overlapped those of sensitive and resistant strains. With 5-μg methicillin disks, clearer separation of strains based on susceptibility to penicillin G occurred. Strains with zones of <35 mm around penicillin G disks and <25 mm around methicillin disks should have penicillin G MICs determined to confirm their resistance to penicillin G. In view of the potential for pneumococci to be resistant to the agents used in this study, antimicrobial susceptibility of all clinically significant isolates should be determined.
Enhancement of post-ultraviolet killing in Escherichia coli K-12 through the action of gyrase inhibitors: evidence for associated gyrase-recBC deoxyribonuclease function
Authors: Purdy M A , Yielding K L
Published: June 2012

This work in conjunction with the results presented in an earlier report (M. A. Purdy and K. L. Yielding, Antimicrob. Agents Chemother. 10:182--184, 1976) showed the following. (i) Nalidixic acid and novobiocin could inhibit post-ultraviolet and post-X-ray survival, implicating gyrase function in deoxyribonucleic acid repair. (ii) The inhibition of post-ultraviolet survival requires the action of functional recBC deoxyribonuclease. (iii) Structural changes in the gyrase could (a) cause recBC mutants to exhibit enhancement of post-ultraviolet killing in the presence of novobiocin, (b) increase the ultraviolet sensitivity of recBC mutants, and (c) enhance the thermal lability of a recBCts mutant.
Activity of semisynthetic penicillins and synergism with mecillinam against Bacteroides species
Authors: Trestman I , Kaye D , Levison M E
Published: June 2012

The minimal inhibitory concentrations (MIC) of six penicillins (ampicillin, carbenicillin, ticarcillin, piperacillin, mezlocillin, and Bay k 4999) against 29 clinical isolates of Bacteriodes spp. (including Bacteroides fragilis, Bacteroides thetaiotaomicron, and Bacteroides vulgatus) were determined by an agar dilution method. Bay k 4999 was most active, followed in descending order by ampicillin, piperacillin, mezlocillin, ticarcillin, and carbenicillin. Mecillinam, a 6 beta-amidino-penicillanic acid, inhibited no strains at 50 micrograms/ml, but when compared with ampicillin, a fourfold or greater increase in MIC for ampicillin (antagonism) was noted in 3 of 29 strains, with no effect on MIC for 26 strains, whereas when combined with carbenicillin, a fourfold or greater decrease in MIC for both antibiotics (synergism) was noted in 12 strains, 4 of which had an MIC of greater than or equal to 250 micrograms/ml for carbenicillin alone. These studies demonstrate the increased activity of some newer semisynthetic penicillins and the potential synergy obtained with mecillinam and carbenicillin against Bacteroides sp.
Phosphonopeptides as antibacterial agents: metabolism and pharmacokinetics of alafosfalin in animals and humans
Authors: Allen J G , Havas L , Leicht E , Lenox-Smith I , Nisbet L J
Published: June 2012

The metabolism and pharmacokinetics of a synthetic antibacterial phosphonodipeptide, alafosfalin, have been studied in rats, baboons, and human volunteers. The compound was rapidly absorbed from the injection site after subcutaneous and intramuscular administration and gave peak plasma concentrations at 15 to 20 min after dosing. Distribution studies showed that high drug concentrations were produced in inflammatory exudates and most tissues except brain. Alafosfalin was rapidly cleared from the general circulation, mainly by the kidney. Plasma half-lives were 20 min in rats and approximately 1 h in baboons and humans. Alafosfalin was well absorbed after oral administration, but was extensively hydrolyzed to alanine and L-1-aminoethylphosphonic acid before it reached the general circulation. This first-pass metabolism was less marked in humans than in animals. Administration of 200-mg intramuscular and 500-mg oral doses produced concentrations of intact phosphonodipeptide in human plasma and urine which were in excess of the in vitro minimal inhibitory concentrations for many pathogenic organisms. The rate of absorption and elimination of alafosfalin in humans were also very similar to published data on beta-lactam antibiotics. This suggests that the pharmacokinetics can be matched to provide synergistic combinations for clinical use.
N-alpha-Cocoyl-L-arginine ethyl ester, DL-pyroglutamic acid salt, as an inactivator of hepatitis B surface antigen
Authors: Sugimoto Y , Toyoshima S
Published: June 2012

N-alpha-Cocoyl-L-arginine ethyl ester, DL-pyroglutamic acid salt (CAE), exhibited a strong inactivating effect on hepatitis B surface antigen. Concentrations of CAE required for 50 and 100% inactivation of the antigen were 0.01 to 0.025% and 0.025 to 0.05% respectively. CAE completely inactivated hepatitis B surface antigen at the lowest concentration compared with various compounds including about 500 amino acid derivatives, sodium hypochlorite, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, and some detergents. Furthermore, CAE inactivated vaccinia virus, herpes simplex virus, and influenza virus, whereas poliovirus was not inactivated at all. The results suggest that the inactivating effects of CAE are related to interaction with lipid-containing viral envelopes.
Comparison of the penicillin-binding proteins of different strains of Neisseria gonorrhoeae
Authors: Nolan R D , Hildebrandt J F
Published: June 2012

This study was undertaken to determine if the categorization of Neisseria gonorrhoeae strains into disseminated gonococcal infection (DGI) and non-DGI types was also paralleled by some common characteristic in their penicillin-binding proteins (PBPs). Fluorography of sodium dodecyl sulfate-containing polyacrylamide gels, on which the [14C]penicillin-labeled PBPs had been separated, was used to visualize the PBPs. No common characteristic PBP for genital or DGI strains was observed. Apart from PBPs 1 and 4, which were observed in all cases, there was an apparently random distribution of other PBPs in both types of N. gonorrhoeae. It was concluded from these data that the penicillin susceptibility associated with most DGI strains of N. gonorrhoeae cannot be correlated with any specific changes in their PBP patterns.
Lytic effect of di- or tricarboxylic acids plus sodium dodecyl sulfate against Pseudomonas aeruginosa
Authors: Adair F W , Geftic S G , Heymann H
Published: June 2012

Pseudomonas aeruginosa was rapidly lysed and killed when treated with several multiple-carboxylic acids at 100 micrograms/ml, followed by exposure to sodium dodecyl sulfate at 5 mg/ml.
Comparison of cefamandole nafate to cefamandole by microbiological assay
Authors: Winely C L , Spears J C , Scott J K
Published: June 2012

Before microbiological assay, cefamandole nafate should be hydrolyzed for 1 h at 37 degrees C in pH 8 buffer (0.1 M) or for 30 min at room temperature in aqueous solutions containing 1.25 molar equivalents of sodium carbonate.