bluuebunny/crossref_metadata_2025 huggingface dataset:
Rosamicin—a New Drug for the Treatment of Bacterial Prostatitis
Authors: Baumueller Axel , Hoyme Udo , Madsen Paul O.
Published: June 2012

Rosamicin, a new macrolide substance, was investigated in dogs and humans with regard to its usefulness for the treatment of bacterial prostatitis and compared with the well-known macrolide erythromycin. In dogs with normal and experimentally infected prostates, concentration ratios for rosamicin in prostatic secretion, interstitial fluid (obtained from implanted tissue chambers), and tissue were significantly higher than for erythromycin. The difference was even more pronounced in human prostatic tissue, obtained by transurethral resection. With its broad spectrum against many common urinary pathogens, rosamicin seems to be a promising drug for the treatment of acute and chronic bacterial prostatitis.
In Vitro Susceptibility Studies with Cefaclor and Cephalexin
Authors: Scheld W. Michael , Korzeniowski Oksana M. , Sande Merle A.
Published: June 2012

The in vitro activity of cefaclor and cephalexin against clinical isolates of four bacterial genera was compared. Both agents had a similar range of activity, but cefaclor was significantly more active by weight than cephalexin for most isolates tested.
Susceptibility of Organisms in the
Mycobacterium fortuitum
Complex to Antituberculous and Other Antimicrobial Agents
Authors: Sanders W. Eugene , Hartwig Eldert C. , Schneider Nathan J. , Cacciatore Robert , Valdez Henry
Published: June 2012

Of 21 antimicrobial agents tested in vitro, amikacin was the most predictably active against clinical isolates belonging to the
Mycobacterium fortuitum
complex; however, only 50% of strains studied were susceptible to clinically attainable concentrations of the drug.
R Plasmids of the S Incompatibility Group Belong to the H2 Incompatibility Group
Authors: Taylor Diane E. , Grant Robert B.
Published: June 2012

Plasmids of the S and H2 incompatibility groups showed thermosensitive transfer and a bacteriophage inhibition phenotype and were incompatible with one another.
Beta-Lactamase Effect on Ampicillin Treatment of
Haemophilus influenzae
B Bacteremia and Meningitis in Infant Rats
Authors: Moxon E. Richard , Medeiros Antone A. , O'Brien Thomas F.
Published: June 2012

Intraperitoneal injections of 250 mg of ampicillin per kg every 6 h for 30 h sterilized the blood and cerebrospinal fluid of infant rats infected with either a β-lactamase-containing strain of
Haemophilus influenzae
type b or a strain lacking the enzyme. However, a single injection of 100 mg/kg sterilized the blood and cerebrospinal fluid of significantly fewer of those rats infected with the β-lactamase-producing strain. The results suggest that resistance of β-lactamase-containing strains of
H. influenzae
in vivo may be inoculum dependent, as demonstrated previously in vitro. The infant rat model appears suited for the quantitative delineation of the effect of β-lactamase on the treatment of
H. influenzae
bacteremia and meningitis with β-lactamase antibiotics.
Penicillinase-Resistant Penicillins Plus Gentamicin in Experimental Enterococcal Endocarditis
Authors: Lincoln Lawrence J. , Weinstein Allan J. , Gallagher Molly , Abrutyn Elias
Published: June 2012

Previous in vitro studies demonstrating that the penicillinase-resistant penicillins act synergistically in combination with gentamicin against some enterococci have suggested that these combinations might be effective therapy for enterococcal infections in vivo. To determine the in vivo effectiveness of such combinations, we treated rabbits with enterococcal endocarditis with gentamicin and either nafcillin, oxacillin, or methicillin. Despite doses of the penicillins equivalent to 12 or 24 g/day in a 70-kg patient, the percentage of animals in each treatment group with sterile valves at autopsy after spontaneous death or sacrifice after 21 days of therapy was low. High-dose therapy with the penicillins did not significantly increase survival over the low-dose treatment groups. Thus, it seems prudent to include penicillin with a penicillinase-resistant penicillin and gentamicin as the initial therapy of patients with endocarditis possibly caused by enterococci.
Factors Governing the Emergence of Resistance to Nalidixic Acid in Treatment of Urinary Tract Infection
Authors: Greenwood David , O'Grady Francis
Published: June 2012

Cultures of
Escherichia coli
were exposed to nalidixic acid in an in vitro model in which the conditions of drug-organism interaction resembled those of bacterial cystitis treatment. Results obtained in this way suggested that emergence of bacterial resistance should not be a major problem in treatment of uncomplicated urinary infection; such cases might indeed respond to a less intensive course of treatment than is usual. More prolonged, high-dosage therapy with nalidixic acid may be required for patients with more complicated infections if the risk of failure from the emergence of bacterial resistance is to be minimized.
In Vitro Susceptibility of
Nocardia asteroides
to Amikacin
Authors: Dalovisio Joseph R. , Pankey George A.
Published: June 2012

By drug dilution tests in agar, it has been shown that each of 27 strains of
Nocardia asteroides
was inhibited by 1 μg or less of amikacin per ml of medium.
Absence of Strand Breaks in Deoxyribonucleic Acid Treated with Metronidazole
Authors: LaRusso Nicholas F. , Tomasz Maria , Kaplan David , Müller Miklós
Published: June 2012

The deoxyribonucleic acid (DNA)-degrading potential of metronidazole was evaluated in vitro by three techniques: determination of melting curve, measurement of viscosity, and centrifugation in neutral or alkaline sucrose gradients. Studies were performed on calf thymus DNA and on
3
H-labeled or unlabeled pneumococcal and T7 phage DNA after treatment with metronidazole alone or metronidazole reduced by sodium dithionite in the presence of DNA. This latter process is known to elicit covalent binding of metronidazole to DNA. Reduced or unreduced metronidazole had no effect on the melting properties, viscosity, or sedimentation velocity of the nucleic acids studied. Sodium dithionite alone, however, caused a 25% decrease in the intrinsic viscosity of pneumococcal DNA, and decreased the sedimentation velocity of pneumococcal and T7 phage DNA in both neutral and alkaline sucrose gradients. These data suggest that degradation of DNA is not important in the interaction of metronidazole with nucleic acids, an interaction assumed relevant to the cytotoxic, radiosensitizing, and mutagenic activities of this compound.
Evaluation of the Micro-Media System for Quantitative Antimicrobial Drug Susceptibility Testing: a Collaborative Study
Authors: Barry A. L. , Jones R. N. , Gavan T. L.
Published: June 2012

Micro-Media Systems (MMS) has developed a procedure by which microdilution trays can be filled with dilutions of antimicrobial agents, frozen, and distributed to clinical laboratories. The trays are prepared in various distribution centers throughout the United States to supply clinical laboratories in the vicinity of each center. For use, trays are removed from the freezer, allowed to thaw, and then inoculated with inocula prepared as for any other susceptibility test, using a convenient disposable inoculator (ca. 5 μl per well). A collaborative study was planned to evaluate microdilution trays prepared in three Micro-Media Systems distribution centers. Microdilution minimal inhibitory concentrations (MICs) were compared to standard tube dilution tests (the international collaborative study group method). With gram-positive cocci, the two techniques gave essentially equivalent results. With gram-negative bacilli, the microdilution MICs were generally one doubling dilution lower than the standard tube dilution MICs. Similar results were seen with microdilution trays prepared with a Cooke Dynatech MIC 2000. Inter- and intralaboratory reproducibility with the macro- and microdilution techniques were quite satisfactory, i.e., at least 96% of the end points were within a range of ±1 log
2
dilution intervals.
Development of the Agar Disk Method for the Rapid Selection of Cephalosporin Producers with Improved Yields
Authors: Trilli Antonio , Michelini Verardo , Mantovani Vera , Pirt S. John
Published: June 2012

To screen the abilities of mutant strains of
Cephalosporium
to produce cephalosporin C, colonies of the organism were grown on the surface of small (4-mm diameter) disks of agar medium. After incubation of the disks for periods of up to 5 days, the antibiotic contents of the disks were assayed by placing them on agar plates of the assay organism and determining the diameters of the inhibition zones. The amount of nitrogen source in the agar disk medium was used to control the amount of antibiotic produced in the disk and, thus, the sensitivity of screening. The relation of agar disk inhibition zone diameters to log shake-flask titers was linear with short incubation times (2 to 3 days) of the disks, but shifted towards a higher order with prolonged incubation (4 to 5 days). The optimum incubation time for the disks was 4 to 5 days, and then a 15% difference in zone diameters was significant with 10 disks per sample. The minimum difference between the shake-flask titers, which could be detected by the agar disk method with 10 disks per sample, was about 30% with 5 days of incubation for the disks. The results suggest that the shake-flask culture underestimated the degree of improvement in strain productivity.
Treatment of Experimental
Staphylococcus aureus
Endocarditis: Comparison of Cephalothin, Cefazolin, and Methicillin
Authors: Carrizosa Jaime , Santoro Jerome , Kaye Donald
Published: June 2012

The effectiveness of cefazolin in
Staphylococcus aureus
endocarditis has been questioned because of in vitro inactivation by staphylococcal beta-lactamase. Cefazolin, although inactivated in vitro by
S. aureus
beta-lactamase, was as effective as cephalothin in the treatment of left-sided
S. aureus
endocarditis in rabbits. Cefazolin (20 mg/kg every 6 or 8 h), cephalothin (40 mg/kg every 6 h), and methicillin (40 mg/kg every 6 h), administered intramuscularly, were compared in the treatment of left-sided endocarditis caused in rabbits by a highly penicillin-resistant strain of
S. aureus
. The three antibiotics were all effective in reducing titers in vegetations. However, at the dose used, methicillin reduced the titers more rapidly than cephalothin or cefazolin. Cefazolin concentrations in serum were about double those achieved with cephalothin or methicillin. However, cefazolin was only half as active as methicillin and one-eighth as active as cephalothin in vitro in a serum assay. The half life in serum of cefazolin, cephalothin, and methicillin were each about 30 min. Serum bactericidal activities of the three antibiotics were very similar.
Production of an Antibiotic Substance by
Bacillus licheniformis
Within the Digestive Tract of Gnotobiotic Mice
Authors: Ducluzeau R. , Dubos F. , Raibaud P. , Abrams G.D.
Published: June 2012

In monoxenic mice, vegetative cells and spores of
Bacillus licheniformis
were enumerated and in vivo antibiotic production was measured at various levels of the digestive tract and in the feces. The apparent independence of vegetative cell and spore populations in the cecum and feces, as well as the marked fluctuations of these two populations in the stomach and small intestine, suggested that sporulation of
B. licheniformis
and production of antibiotic occur only in the upper levels of the digestive tract. Study of dixenic models wherein
B. licheniformis
was inoculated after
Clostridium perfringens
or
Lactobacillus
sp. or before
Lactobacillus
sp. revealed the simultaneous disappearance of
B. licheniformis
from the stomach and antibiotic from the feces. This strain persisted in the cecum, but only in the form of vegetative cells. These models demonstrate that the activity of the microflora in the upper segments can affect the equilibrium of the microflora throughout the digestive tract.
Turbidimetric Studies of Growth Inhibition of Yeasts with Three Drugs: Inquiry into Inoculum-Dependent Susceptibility Testing, Time of Onset of Drug Effect, and Implications for Current and Newer Methods
Authors: Galgiani John N. , Stevens David A.
Published: June 2012

Susceptibility testing with the broth-dilution visual end-point method is inoculum dependent with miconazole and 5-fluorocystosine, but not with amphotericin B. Turbidimetric measurements of yeast growth in the presence of antifungal drugs were therefore performed. With miconazole and 5-fluorocytosine, over the range of concentrations studied, growth occurred until a plateau phase was reached. With drug present prior to log phase growth, a delayed onset of effect was noted which was proportional to the generation time of the organism. With amphotericin B, in contrast, there was sharp transition with increasing drug concentration from no inhibition to complete arrest of growth, and no relation of onset of effect to generation time. These findings provide a possible explanation of inoculum dependence; i.e., at higher inocula, partially inhibited but growing yeasts become visible at higher drug concentrations. Supporting evidence derives from observations with different starting inocula, varying time of reading end points, and other methods of studying growth inhibition. The delay in miconazole and 5-fluorocytosine effect described suggests that rapid methods of susceptibility testing should be utilized with cultures already in log phase.
Amphotericin B Pharmacokinetics in Humans
Authors: Atkinson Arthur J. , Bennett John E.
Published: June 2012

The pharmacokinetics of amphotericin B were studied in two patients at the conclusion of long-term therapy for disseminated histoplasmosis. The distribution kinetics of this drug were adequately described by a three-compartment mamillary model with a total distribution volume averaging 4 liters/kg. The elimination phase half-life of amphotericin B was approximately 15 days, reflecting slow release of amphotericin B from a peripheral compartment. In accordance with previous reports, renal excretion accounted for only 3% of total amphotericin B elimination. The pharmacokinetic model for one of the patients also was used to compare the simulated amphotericin B serum levels that would be expected if initial therapy followed two recommended regimens.
Isolation of Beta-Lactamase from a Penicillin-Susceptible Strain of
Staphylococcus aureus
Authors: Sachithanandam S. , Lowery D. L. , Saz A. K.
Published: June 2012

It is generally accepted that strains of
Staphylococcus aureus
which are susceptible to penicillin G do not produce β-lactamase. However, we have found that such a strain susceptible to 0.06 μg of penicillin per ml and 0.56 μg of methicillin per ml produces β-lactamase(s) which hydrolyzes penicillin G, methicillin, 6-aminopenicillanic acid, and probably cephaloridine. The enzyme which is found only during very early log phase of the growth cycle is not inducible either by penicillin or methicillin and is cell bound and liberated only by disruption of the cell. The rate of enzymatic hydrolysis of methicillin was 60% that of benzylpenicillin. This finding suggests that the elaboration per se of β-lactamase does not necessarily afford resistance to penicillin in this gram-positive-producing cell.
Common Plasmid Specifying Tobramycin Resistance Found in Two Enteric Bacteria Isolated from Burn Patients
Authors: Elwell Lynn P. , Inamine Julia M. , Minshew Barbara H.
Published: June 2012

Tobramycin-resistant burn wound isolates of
Klebsiella pneumoniae
and
Enterobacter cloacae
, together with
Escherichia coli
K-12 transconjugants from these two strains, were examined for plasmid deoxyribonucleic acid (DNA). All the resistant strains contained a common, high-molecular-weight, covalently closed circular DNA plasmid that was absent in the tobramycin-susceptible
E. coli
recipient strain. The common plasmid residing in
E. cloacae
was designated pIE098, and that residing in
K. pneumoniae
was designated pIE099. Both plasmid species were found to have a molecular mass of approximately 60 × 10
6
daltons and a guanine-plus-cytosine content of 50 mol%. The DNA that was extracted from all of the tobramycin-resistant strains tested was able to hybridize to 86 to 100% with pIE098 and pIE099 [
3
H]DNA generated by
Eco
RI to produce fragments of a size similar to those generated by
Bam
HI. This study illustrates the usefulness of simple screening methods for antibiotic resistance plasmids in a hospital epidemiological situation.
Comparative distribution of gentamicin, tobramycin, sisomicin, netilmicin, and amikacin in interstitial fluid in rabbits
Authors: Carbon C , Contrepois A , Lamotte-Barrillon S
Published: June 2012

We compared the penetration of five aminoglycosides into interstitial fluid (IF). IF was obtained in rabbits from Silastic tissue cages. Intramuscular injections were made: 1.5 mg/kg per dose for gentamicin (G), tobramycin (T), sisomicin (S), and netilmicin (N) and 7.5 mg/kg per dose for amikacin (A). Serum levels and IF concentrations were studied for 12 h after a single injection. IF levels were also compared in a six-injection study (one injection every 8 h). Peak serum levels were significantly higher with A than with G, T, S, and N, which gave similar concentrations. In IF, G gave the highest levels 1 h after the first injection. At 4 and 8 h, the concentrations achieved with G and A were similar but significantly greater than those achieved with T, S, and N. Twelve hours after a single injection, N gave higher IF levels than the other drugs except A. In the six-injection study, the IF levels of G and A reached 4.6 +/- 1.5 and 5.27 +/- 1.1 microgram/ml, respectively, at 48 h. S and N gave identical concentrations (2.07 +/- 0.25 and 2.42 +/- 0.42 microgram/ml, respectively). T induced the lowest levels (1.17 +/- 0.30 microgram/ml). Thus, in this rabbit model, the IF concentrations achieved with G and A were above the minimal inhibitory concentrations for most susceptible strains. Possible relations between IF aminoglycoside concentrations and therapeutic efficiency or toxicity are pointed out but deserve further studies.
In vivo susceptibility of the Legionnaires disease bacterium to ten antimicrobial agents
Authors: Lewis V J , Thacker W L , Shepard C C , McDade J E
Published: June 2012

The susceptibility of the Legionnaires disease bacterium to various antimicrobial agents was determined by inoculation of embryonated eggs via the yolk sac. When administered prophylactically, the minimal dose of drug preventing all deaths due to the infection was as follows: rifampin, 0.02 mg; gentamicin, 0.25 mg; streptomycin, 0.39 mg; erythromycin, 0.62 mg; sulfadiazine, 1.56 mg; chloramphenicol, 2.50 mg; and cephalothin, 20.0 mg. Smaller amounts delayed deaths, and larger or equal amounts rendered the embryos free of infection. Oxytetracycline in the largest tested amount, 5.0 mg, protected 80% of the embryos from death, and as little as 0.31 mg delayed death. Chlortetracycline (0.50 mg) and ampicillin (10.0 mg) were ineffective. The six most effective drugs were studied in an experiment in which they were administered at various times after infection in doses that were twice the minimal prophylactic dose preventing all deaths. In this therapeutic experiment, rifampin, and erythromycin allowed 100% survival when given even 72 h after infection; gentamicin, streptomycin, sulfadiazine, and chloramphenicol did so when given 48 h after infection. All six drugs increased mean survival time when administered 72 h after infection.
Antimicrobial activity of metronidazole in anaerobic bacteria
Authors: Tally F P , Goldin B R , Sullivan N , Johnston J , Gorbach S L
Published: June 2012

The antimicrobial activity of metronidazole was investigated in anaerobic bacteria by use of time-viability studies. This antimicrobial agent has a rapid onset of bactericidal activity under proper reducing conditions. The bactericidal rates were not affected by inoculum size or nutritional requirements, nor by inhibition of growth and protein synthesis by chloramphenicol. Using supernatant fractions of actively growing cultures of susceptible organisms, we observed a disappearance of metronidazole and a loss of biological activity, but there was no significant change in preparations from resistant bacteria. The decrease in drug concentration with susceptible cells occurred during the time that its bactericidal action was being exerted. Extracts from susceptible organisms rapidly reduced the concentration of metronidazole, confirming previous observations which suggest that the drug acts as a terminal electron acceptor. Radioisotope experiments with [14C]metronidazole revealed that the compound was taken up by both resistant and susceptible bacteria, although there was a difference in rate and extent of accumulation. These studies demonstrate that metronidazole's antimicrobial activity against anaerobic bacteria is bactericidal and independent of growth rate, and that it involves the uptake and metabolism of the compound.
Comparative effects of sulfones and rifampin on growth of Mycobacterium lepraemurium in macrophage diffusion chamber cultures
Authors: Rightsel W A , Sawyers M F , Peters J H
Published: June 2012

A cell-impermeable diffusion chamber technique has been developed that lends itself to growth studies of Mycobacterium lepraemurium. This technique, in which the organism grows within macrophage cultures inside the chambers that are maintained on monolayer cultures of macrophages, provides a method for a strict in vitro evaluation of antileprosy drugs without the influence of a multiplicity of host factors. This system was used to compare the effect of three sulfone derivatives and rifampin on the growth of M. lepraemurium within these diffusion chamber cultures. Two sulfones, 4,4'-diaminodiphenyl sulfone and 4,4'-diacetamidodiphenyl sulfone, as well as rifampin, suppressed the growth of M. lepraemurium, but monoacetyl sulfone 4-amino-4'acetamidodiphenyl sulfone had no effect. The results indicate that the diffusion chamber technique can be used to evaluate the inhibitory effect of antileprosy drugs on the growth of M. lepraemurium. Also, the method provides for the first time a relatively rapid in vitro method for directly comparing the effects of drugs or their analogs when outside the metabolic influence of an animal host. This technique may be a useful tool for chemotherapy studies with other antileprosy compounds.
Comparative in vitro studies of nalidixic acid, oxolinic acid, and a new analog with thieno (2,3-b) pyridine structure
Authors: Gilis P M , Haemers A , Pattyn S R
Published: June 2012

Bacterial susceptibility to a new organic acid related to nalidixic acid and oxolinic acid was tested. The in vitro susceptibility pattern of the new compound was found to be very similar to that of nalidixic acid.
Interference of granulocyte function by the vehicle of miconazole
Authors: Lee C , Maderazo E G
Published: June 2012

The vehicle of miconazole inhibited adherence and leukotaxis, but did not affect nitroblue tetrazolium reduction and trypan blue exclusion by granulocytes at 0.33% concentration and above.
Chloramphenicol Resistance in
Streptococcus pneumoniae:
Enzymatic Acetylation and Possible Plasmid Linkage
Authors: Dang-Van Annie , Tiraby Gerard , Acar Jacques F. , Shaw William V. , Bouanchaud Daniel H.
Published: June 2012

Clinical isolates of
Streptococcus pneumoniae
resistant to chloramphenicol were observed in France for the first time in 1973. During a 4-year survey, these strains were found to represent 6% of a total of 564 isolates of
S. pneumoniae
in a general hospital and to belong to 13 different serotypes. One such strain, referred to as BM 6001, was shown to inactivate chloramphenicol, and the process was found to be inducible. The inactivated products were demonstrated to be
O
-acetoxy esters of chloramphenicol. The synthesis of an inducible chloramphenicol acetyltransferase was shown to be responsible for the inactivation of the drug. The resistant strain was able to transfer the chloramphenicol marker by transformation to competent strains of pneumococci at a frequency of 1% of that observed for control chromosomal markers. The loss of resistance was enhanced by ethidium bromide treatment, but no chloramphenicol-resistant mutant was isolated by mutagenesis of a “cured” clone or naturally susceptible isolates. All attempts to isolate plasmid deoxyribonucleic acid as covalently closed circular molecules from strain BM 6001 have been unsuccessful, but epidemiological evidence and the fact that the genes specifying chloramphenicol acetyltransferase synthesis are usually located on plasmids suggest that this marker may be plasmid-borne in
S. pneumoniae
.
Factors Influencing Susceptibility of
Nocardia
Species to Trimethoprim-Sulfamethoxazole
Authors: Bennett John E. , Jennings Anne E.
Published: June 2012

Demonstration of synergism between trimethoprim and sulfamethoxazole against 10
Nocardia
isolates was found to be critically dependent upon the isolate, the duration of incubation, and the trimethoprim-sulfamethoxazole ratio. Inoculum effect was not significant. The trimethoprim-sulfamethoxazole ratio in the commercial, fixed-dose combination was found to contain too little trimethoprim to be optimal for
Nocardia
.
Synergism of Fosfomycin-Ampicillin and Fosfomycin-Chloramphenicol Against
Salmonella
and
Shigella
Authors: Perea E. J. , Torres M. A. , Borobio M. V.
Published: June 2012

Ninety strains of
Salmonella
and 50 strains of
Shigella
were tested for susceptibility to fosfomycin, chloramphenicol, and ampicillin by the agar dilution method. Drug interaction between fosfomycin-ampicillin and fosfomycin-chloramphenicol was studied by the agar dilution method. The fractional inhibitory concentration was calculated. The combination of fosfomycin-ampicillin was synergistic against
Salmonella
in 74 cases, additive in 7, indifferent in 7, antagonistic in none, and nonevaluable in 2; against
Shigella
it was synergistic in 27 cases, additive in 9, indifferent in 14, and antagonistic in none. The combination of fosfomycin-chloramphenicol was synergistic against
Salmonella
in 56 cases, additive in 9, indifferent in 13, nonevaluable in 12, and antagonistic in none; against
Shigella
it was synergistic in 29 cases, additive in 10, indifferent in 9, nonevaluable in 2, and antagonistic in none. Killing curves with combinations of each antimicrobial agent showed that the cultures that had proven to be indifferent by the agar dilution method showed a bactericidal effect until h 4, with posterior regrowth of the culture after this time period. For the strains in which synergism was demonstrated, total bactericidal activity was reached at 24 h.
Chloramphenicol Resistance Plasmids in
Escherichia coli
Isolated from Diseased Piglets
Authors: Jørgensen Sigrid Tue
Published: June 2012

The plasmids in 19 chloramphenicol-resistant
Escherichia coli
strains of three pig pathogenic antigen types were studied in conjugation and transduction experiments. The plasmids had identical resistance patterns: streptomycin, spectinomycin, sulfonamides, and chloramphenicol (Sm, Sp, Su, Cm) and belonged to IncFII. One plasmid carried ampicillin resistance in addition. Restriction enzyme analysis of the deoxyribonucleic acid from five of the plasmids originating from the same herd showed that their digestion patterns with
Eco
RI were indistinguishable.
Eco
RI cleaved the deoxyribonucleic acid of a sixth plasmid from the same herd and displayed nine of the ten bands of the other five plasmids plus an additional six. It appears that the five plasmids with identical restriction patterns have a common origin and may be copies of the same plasmid from which the sixth may have developed. Four strains carried two plasmids each. In two of these strains, a plasmid with a tetracycline marker (Tc), or possibly the tetracycline marker alone, recombined frequently with the Sm Sp Su Cm plasmid without destroying any known function of the latter. The possibility that Tc is carried on a translocation sequence is discussed.
In Vitro Evaluation of a Semisynthetic Derivative of Gentamicin B (SCH 21420)
Authors: Yu Pauline K. W. , Washington John A.
Published: June 2012

The activities of Sch 21420 and amikacin were compared in vitro against 448 clinical bacterial isolates and against 82 gentamicin-resistant isolates of gram-negative bacilli. At 1 μg/ml, Sch 21420 was more active than amikacin against most
Enterobacteriaceae
but less active against
Pseudomonas aeruginosa
. Activity of these antibiotics against gentamicin-resistant organisms varied according to the species examined.
Haemophilus influenzae
Susceptibility Testing Within Four Hours by a Modification of the Autobac I System
Authors: Hosmer Marion E. , Sprunt Katherine
Published: June 2012

By adding an XV strip to the eugonic broth or substituting Levinthal broth, the standard Autobac I susceptibility testing system may be used to determine susceptibility of
Haemophilus influenzae
to antimicrobial agents. Complete concordance was attained in testing 30 strains (5 resistant) by Autobac I, disk diffusion, and broth dilution methods. Autobac I results were available within 4 h after isolation of the organism.
Streptomycin and Spectinomycin Resistance Mediated by Plasmids
Authors: Kawabe Haruhide , Tanaka Tokumitsu , Mitsuhashi Susumu
Published: June 2012

Resistance to tetracycline (Tc), chloramphenicol (Cm), streptomycin (Sm), and sulfanilamide (Sa) was surveyed in clinical isolates of
Escherichia coli
and
Shigella
strains. Among the Sm Sa-resistant strains, the frequency of nonconjugative r (Sm Sa) plasmids was much higher than that of conjugative R plasmids encoding double resistance. The biochemical mechanism of Sm resistance mediated by the conjugative plasmids R(Tc Cm Sm Sa) and R(Cm Sm Sa) and about half the numbers of conjugative R(Tc Sm Sa) and R(Sm Sa) plasmids tested were found to be due to adenylylation of the drug. The remaining conjugative R(Tc Sm Sa) and R(Sm Sa) plasmids and all nonconjugative (Sm Sa) plasmids tested inactivated Sm by phosphorylation.
Killing of Intraphagocytic
Staphylococcus aureus
by Dihydrostreptomycin Entrapped Within Liposomes
Authors: Bonventre Peter F. , Gregoriadis Gregory
Published: June 2012

Liposomes (phospholipid vesicles) may serve as vehicles of antibiotic transport to intracellular sites. Liposomes containing entrapped dihydrostreptomycin enhanced killing of
Staphylococcus aureus
contained within phagocytic vacuoles.
Susceptibility of
Staphylococcus aureus
to Cefaclor and Cephalothin: Laboratory and Clinical Studies
Authors: Gray Barry M. , Hubbell Carol A. , Dillon Hugh C.
Published: June 2012

In vitro susceptibility tests of 201 strains of
Staphylococcus aureus
by agar dilution revealed 90% to be susceptible to 8 μg or less of cefaclor per ml. Strains from hospitalized children and adults were more often resistant than those from patients with bullous impetigo. Cephalothin was more active than cefaclor against all strains tested. Results with disk tests, including those strains examined from the clinical investigation, revealed some discrepancies in identifying strains more resistant to cefaclor. In clinical studies, cefaclor proved quite effective for the treatment of bullous impetigo. Of 73 patients, 90% were cured and 7% improved after completing 5 or more days of treatment. Prompt improvement was noted among most patients seen 3 to 5 days after treatment was begun. One patient experienced mild diarrhea. There were no other adverse or toxic manifestations attributable to therapy.
Effects of Hydration on Gentamicin Excretion and Renal Accumulation in Furosemide-Treated Rats
Authors: Chiu Peter J. S. , Long James F.
Published: June 2012

The effect of furosemide on gentamicin excretion and tissue accumulation was studied with clearance techniques in anesthetized rats, at two different infusion rates of saline or Ringer solution. Gentamicin (∼20 mg/kg) was administered by constant intravenous infusion over a period of 3 h. With the low fluid infusion rate, furosemide (25 mg/kg intravenously) caused severe reduction in glomerular filtration rate and diminished urinary output of gentamicin. Serum and renal tissue levels of the antibiotic were significantly elevated. High fluid infusion prevented the decline of the glomerular filtration rate, with near normalization of all measurements. A fluid deficit incurred by furosemide was noted at both the low and high infusion rates. Complete correction of this fluid deficit by continuous adjustment of the infusion rate fully restored normal renal handling of gentamicin. These results suggest that furosemide had no direct effect on renal excretion of gentamicin. In comparison, renal handling of gentamicin in rats did not respond to changes in the rate of fluid infusion in the absence of furosemide therapy. It appears that gentamicin excretion and gentamicin accumulation in the renal cortex in furosemide-treated rats, in contrast with those in untreated rats, are influenced significantly by the rate of fluid infusion. Fluid administration sufficient to maintain the glomerular filtration rate was found to be necessary for appropriate gentamicin elimination, with consequent reduction in serum and renal tissue levels of the drug.
Antimalarial Activities of Various 9-Phenanthrenemethanols with Special Attention to WR-122,455 and WR-171,669
Authors: Schmidt L. H. , Crosby Ruth , Rasco Jane , Vaughan Dennis
Published: June 2012

Pilot appraisals of the activities of 16 specially selected 9-phenanthrenemethanols against acute infections with
Plasmodium falciparum
in owl monkeys showed that all were more active than the reference compound, WR-33,063. WR-122,455, the most active derivative, and WR-171,669, ranked sixth, were selected for study in human volunteers. To assist this undertaking, appraisals of both compounds in owl monkeys infected with various strains of
P. falciparum
were expanded. These assessments showed: (i) that WR-122,455 was four times as active as chloroquine against infections with chloroquine-sensitive strains and that WR-171,669 equalled chloroquine in activity; (ii) that these compounds were fully active against infections with strains resistant to chloroquine, pyrimethamine, or quinine, or to all three standard drugs; (iii) that the activity of WR-122,455 was a function of total dose, single doses being as effective as the same amounts delivered in three or seven daily fractions; and (iv) that a single dose of WR-122,455 conferred extended, although only partial, protection against challenges with trophozoites. Complementary experiments in rhesus monkeys inoculated with sporozoites of
P. cynomolgi
showed that the activity of WR-122,455 was limited to blood schizonts and did not extend to early or late tissue schizonts. These evaluations were compatible with the results of preliminary studies of the activities of WR-122,455 and WR-171,669 in human volunteers.
Patient Variables Associated with Penicillin Resistance in
Neisseria gonorrhoeae
Authors: Thornsberry Clyde , Jaffe Harold W. , Reynolds Gladys H. , Zaidi Akbar A. , Wiesner Paul J.
Published: June 2012

In an ongoing cooperative study of uncomplicated genital gonorrhea within the United States, 6,735 pretreatment gonococcal isolates were tested for their in vitro resistance to penicillin. By using a regression analysis technique, we examined 99 patient-associated variables which might be associated with penicillin resistance of the isolates. Patients were most likely to have relatively resistant isolates if they were black, had used antimicrobial agents within 2 weeks of treatment for gonorrhea, or were men with symptomatic urethritis.
Therapeutic Effect of Trisodium Phosphonoformate on Cutaneous Herpesvirus Infection in Guinea Pigs
Authors: Alenius Stefan , Dinter Zvonimir , Öberg Bo
Published: June 2012

When applied topically, trisodium phosphonoformate (PFA) displayed activity against established cutaneous herpesvirus infections in guinea pigs similar to that exhibited by the closely related phosphonoacetic acid (PAA); however, unlike PAA, PFA was not locally skin irritating. The therapeutic benefits of topical application of PFA were clearly evident when application was delayed for 48 h after virus inoculation, at which time lesions were well developed. The therapeutic effect was dependent on the concentration of PFA and the duration of treatment. PFA exhibited significant activity against established infections when administered intraperitoneally, although it was less effective via this systemic route than when applied topically.
Antimalarial Activities of Various 4-Pyridinemethanols with Special Attention to WR-172,435 and WR-180,409
Authors: Schmidt L. H. , Crosby Ruth , Rasco Jane , Vaughan Dennis
Published: June 2012

Pilot appraisals of the activities of 10 specially selected 2,6-substituted-4-pyridinemethanols against acute
Plasmodium falciparum
infections in owl monkeys identified three derivatives that were two to three times as active as chloroquine against infections with a 4-aminoquinoline-susceptible strain and, at the same doses, were equally effective against infections with a strain fully resistant to treatment with maximally tolerated doses of chloroquine, quinine, and pyrimethamine. Two of these derivatives, WR-172,435 and WR-180,409, deemed worthy of evaluation in human volunteers, were studied in greater depth in owl monkeys infected with either the multidrug-resistant Smith strain of
P. falciparum
or the pyrimethamine-resistant Palo Alto strain of
P. vivax
. These studies showed (i) that at the same total oral dose, 3-day and 7-day treatment schedules were equally effective and slightly superior to a single-dose schedule; (ii) that WR-172,435 was slightly more active than WR-180,409 in each treatment regimen; (iii) that intravenous delivery of WR-180,409 phosphate was feasible and effective; (iv) that both compounds effected control of parasitemia more rapidly than any standard or newly discovered antimalarial drug; and (v) that WR-172,435 and WR-180,409 had therapeutic indexes at least four to eight times those exhibited by chloroquine in infections with 4-aminoquinoline-susceptible strains, indexes retained by these pyridinemethanols against infections with various drug-resistant strains.
Purification and the Ultrastructure of a Bacteriocin Produced from
Shigella sonnei
Strain 100052
Authors: Amako Kazunobu , Matsuguchi Motoyuki , Takeya Kenji , Tatsuta Emiko , Takagi Yasuyuki
Published: June 2012

A bacteriocin produced by strain 100052 of
Shigella sonnei
(shigellacin 52) was purified about 80-fold from a mitomycin C-induced culture supernatant. The purified preparation gave a single band on sodium dodecyl sulfate-gel electrophoresis with an approximate molecular weight of 10,000. The negatively stained electron micrograph of the purified bacteriocin preparation revealed the existence of three different particles. They were a small cylindrical tube (4.2 by 6.0 nm), a ring-shaped particle and a filamentous structure. The molecular weight calculated from the shape of the small tube was approximately 50,000. The latter two particles appeared to be constructed from subunits which were morphologically similar to the cylindrical tube. These results suggested that the morphological subunit of shigellacin 52 consisted of five chemical subunits with molecular weights of 10,000 each, and it assembled into two types of polymers, a ring-shaped particle and a filamentous structure, which seemed to be the main components of the purified shigellacin 52 preparation.
Pharmacokinetics of Amoxicillin and Ampicillin: Crossover Study of the Effect of Food
Authors: Eshelman Fred N. , Spyker Daniel A.
Published: June 2012

The effect of food on the absorption of amoxicillin and ampicillin was studied in 16 normal subjects in a double-blind crossover study after each subject was given a single oral 500-mg dose. Serum drug levels were analyzed, assuming a one-compartment linear model with first-order absorption and absorption delay, area under the curve, and urinary recovery. Variations in kinetic parameters were examined by using analysis of variance. The results showed little or no effect of fasting versus nonfasting on amoxicillin absorption, as evidenced by peak serum levels (8.9 μg/ml, fasting, 8.8 μg/ml, nonfasting), area under the curve (26.9 μg/ml per 70 kg, fasting, 22.2 μg/ml per 70 kg, nonfasting), and urinary recovery (47%, fasting; 44%, nonfasting). Ampicillin absorption was significantly decreased in the nonfasted group by the same parameters (peak level: 5.4 μg/ml, fasting, 4.0 μg/ml, nonfasting; area under the curve, 17.4 h·μg/ml, fasting, 12.0 h·μg/ml, nonfasting; urinary recovery, 37%, fasting, 29%, nonfasting). These results confirm the reliable absorption of orally administered amoxicillin in the fed as well as the fasted state.
Comparison of Netilmicin and Amikacin in Treatment of Complicated Urinary Tract Infections
Authors: Maigaard Svend , Frimodt-Möller Niels , Madsen Paul O.
Published: June 2012

Netilmicin and amikacin, two recently developed aminoglycosides, were compared in a prospective, randomized study of 57 male patients with complicated urinary tract infections. Both drugs were administered intramuscularly every 12 h for 7 to 10 days, netilmicin at 2 mg/kg and amikacin at 7.5 mg/kg. The two groups were comparable as to infecting bacteria and underlying pathology of the urinary tract. No patients had indwelling catheters. All microorganisms isolated were sensitive to both antibiotics. A total of 69% of the patients treated with netilmicin and 57% of the patients treated with amikacin were cured of the infection, as defined by a negative culture at 7 days after discontinuation of treatment. No major side effects were recorded, and no significant changes were noted in parameters of renal function. Of the patients treated with amikacin, 21% experienced temporary local pain at the injection site; no such effect was noted in the netilmicin-treated group. Therefore, netilmicin appeared to be as effective and better tolerated than did amikacin in the treatment of complicated urinary tract infection.
Effect of Enzymatic Adenylylation on Dihydrostreptomycin Accumulation in
Escherichia coli
Carrying an R-Factor: Model Explaining Aminoglycoside Resistance by Inactivating Mechanisms
Authors: Dickie P. , Bryan L. E. , Pickard M. A.
Published: June 2012

Strains of
Escherichia coli
carrying R-factor R71(a), which codes for a streptomycin-spectinomycin adenylyltransferase, have elevated levels of resistance to dihydrostreptomycin (DHS) compared with isogenic R
−
bacteria. DHS accumulated by whole cells and spheroplasts of R
+
bacteria is lower than that observed for R
−
strains, a result of the absence of the second and more rapid of the two energy-dependent phases of DHS uptake seen in susceptible
E. coli
. A mutant of R
+
E. coli
with reduced DHS resistance has been shown to have reduced levels of streptomycin-spectinomycin adenylyltransferase activity as well as enhanced drug accumulation. Actively accumulated DHS was recovered from R
+
cells as the adenylylated derivative. Neither was inactivated antibiotic detected in culture filtrates, nor was actively accumulated drug lost from R
+
cells under normal conditions. The cellular distribution of actively accumulated DHS in R
+
and R
−
cells was found to be the same. Membranes isolated from these cells retained only a small fraction (≃1%) of the total cell-associated drug. The R
+
derivative of a mutant with defective energy transduction (
E. coli
NR-70) and reduced ability to transport aminoglycosides has a significantly higher minimal inhibitory concentration of DHS than its R
+
parent (strain 7). Streptomycin-spectinomycin adenylyltransferase activity, from comparisons of

K
m

values and total activities of enzyme, was the same in both strains. The enzyme has been localized to the exterior surface of the bacterial inner membrane, although isolated membranes lacked detectable enzyme activity. The preceding observations are consistent with the proposal that the level of R71(a)-mediated DHS resistance is the outcome of competition between the rate of adenylylation and the rate of the first energy-dependent phase of DHS transport. When the rate of adenylylation exceeds the first energy-dependent phase, adenylylated DHS is accumulated, apparently in a manner identical to the accumulation of DHS. Unlike DHS, adenylylated DHS does not interact with ribosomes, and, consequently, there is a failure to initiate ribosomally dependent sequelae such as the second energy-dependent phase of accumulation, inhibition of protein synthesis, and/or misreading of mRNA.
Effect of Antibiotics on Protease Production by a Viridans Streptococcus
Authors: Straus David C. , Mattingly Stephen J. , Milligan Thomas W.
Published: June 2012

A viridans streptococcus (
Streptococcus
MG
intermedius
974) isolated from a confirmed case of subacute bacterial endocarditis was studied for the production of extracellular proteases during exponential growth and after penicillin (0.10 μg/ml) and/or streptomycin (20 μg/ml) treatment. Exponentially growing cultures produced a variety of extracellular proteases, as determined by the elution profiles of active proteins from Sephadex G-100 and Sepharose 4B columns. Examination of supernatant fluids from cultures of
S
. MG
intermedius
treated with penicillin or streptomycin for 12 h indicated a reduction of at least 50% in the number of different proteolytic species produced. However, some of the proteases produced by the cultures during penicillin or streptomycin treatment had significantly higher specific activities when compared with proteases produced by exponentially growing cells. The combination of penicillin and streptomycin further reduced both the number and the specific activities of the extracellular proteases on a cell dry weight basis.
Concentration Relationships of Cefaclor in Serum, Interstitial Fluid, Bile, and Urine of Dogs
Authors: Waterman Norton G. , Scharfenberger Louis F.
Published: June 2012

The concentrations of cefaclor in the serum, urine, bile, and tissue fluids of the abdominal wall, kidney, and liver of dogs were compared over a 4-h period after oral administration of a single dose of this drug. The concentration of cefaclor in the soft-tissue interstitial fluid peaked 2 h after administration, thereby demonstrating a diffusion rate similar to those of other cephalosporins. Both urine and bile concentrations greatly exceeded the serum levels, whereas none of the tissue fluid concentrations were greater than the serum concentrations at the times of measurement.
Susceptibility of
Eikenella corrodens
to Ten Cephalosporins
Authors: Goldstein Ellie J. C. , Sutter Vera L. , Finegold Sydney M.
Published: June 2012

The susceptibility of 24 strains of
Eikenella corrodens
was determined, by the agar dilution technique, to 10 cephalosporins, as well as to clindamycin, penicillin and dicloxacillin. All strains were uniformly very susceptible to penicillin G and cefoxitin and resistant to clindamycin and dicloxacillin. Cefazolin showed good activity. Cephalexin, cephradine, and cefadroxil showed poor activity, and cefamandole's activity was relatively poor. Cephalothin, cephapirin, cefaclor, and cephaloridine showed moderate activity, with some strains relatively resistant.