bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Gonorrhea with Spectinomycin Hydrochloride: Comparison with Standard Penicillin Schedules
Authors: Duncan W. Christopher , Holder William R. , Roberts David P. , Knox John M.
Published: June 2012

Spectinomycin hydrochloride, a new parenteral antibiotic prepared from
Streptomyces spectabilis
, was compared with standard U.S. Public Health Service-recommended dosages of aqueous procaine penicillin G in the treatment of uncomplicated gonorrhea in 353 men and 314 women. Of the 314 women, 130 had a pretreatment positive rectal culture. All diagnoses were proven by culture on Thayer-Martin selective medium. Minimal inhibitory concentrations of both drugs were determined. Single doses of 2 and 4 g of spectinomycin were compared with 2.4 million units of procaine penicillin in males and with both 2.4 and 4.8 million units of procaine penicillin in females. Both spectinomycin schedules, 2.4 million units of penicillin in males and 4.8 million units of penicillin in females, resulted in cure rates in excess of 90%. There were no failures at the rectal site only in those women with positive rectal cultures. There was no advantage to using the larger amount of spectinomycin in either sex.
Origin of Glycine from Acid Hydrolysis of the β-Lactam Antibiotic A16886B
Authors: Brannon D. R. , Mabe J. A. , Ellis R. , Whitney J. G. , Nagarajan R.
Published: June 2012

Structural analysis of two new β-lactam antibiotics, A16884A and A16886B, indicated that they, like cephalosporin C, were composed of modified valine and cysteine residues, and α-aminoadipic acid. However, acid hydrolysis of A16886B and A16884A produced three times as much glycine as did hydrolysis of cephalosporin C under the same conditions. Samples of A16886B-
14
C-6
and A16886B-
14
C-8
were prepared by the addition of cysteine-
14
C-3
and cystine-
14
C-1
to fermentations of
Streptomyces clavuligerus
. The specific activity of glycine obtained from hydrolysis of A16886B-
14
C-6
was considerably higher than that from hydrolysis of A16886B-
14
C-8
. An explanation for the difference in amounts of glycine obtained from hydrolysis of these antibiotics is discussed.
Serum Sulfonamide Concentration After Oral Administration: Comparison of Results of Chemical Assay with Two Bioassay Techniques
Authors: Berman Harris A. , Barza Michael , Weinstein Louis
Published: June 2012

Sulfonamide concentrations were studied in 210 serum samples from 10 volunteers after ingestion of sulfacytine, sulfisoxazole, and sulfadiazine. Results obtained by chemical assay were compared with bioassay values determined by two techniques: twofold broth dilution and agar diffusion. Although the correlation for individual samples was rather poor for the twofold broth-dilution method, the agar-diffusion bioassay correlated well with chemical determinations. The agar-diffusion assay tended to “underread” the chemical assay by an amount characteristic of each drug.
Resistance of Group A Beta-Hemolytic Streptococci to Lincomycin and Erythromycin
Authors: Dixon J. M. S. , Lipinski A. E.
Published: June 2012

Ten (0.05%) of 18,628 strains of
Streptococcus pyogenes
isolated from clinical specimens in the 3 years 1968 to 1970 were resistant to lincomycin and erythromycin. All 10 strains were highly resistant to lincomycin, having minimal inhibitory concentration (MIC) values of 200 μg/ml. There were two degrees of resistance to erythromycin: four strains were highly resistant, having MIC values of 200 μg or more/ml; and six strains showed slight resistance, MIC values being 0.78 to 1.56 μg/ml. There was no known epidemiological relationship between any of the patients infected with the resistant strains, which belonged to a variety of T serotypes. A zonal pattern of resistance to lincomycin occurred in four strains, all of which were only slightly resistant to erythromycin. After incubation for 24 hr in a twofold dilution series of lincomycin in broth, the strains grew in 0.05 μg or less/ml and in 50 and 100 μg/ml, but not in intermediate concentrations. Tests in agar indicated that the bacterial population of one strain, but not of the other three, was homogeneous in respect to its ability to grow readily in low and high, but not in intermediate, concentrations. The zone phenomenon is of significance in the clinical laboratory, since unawareness of it might result in a highly resistant strain being regarded as susceptible to lincomycin in tube or plate MIC tests that do not include sufficiently high concentrations of lincomycin.
Tobramycin: In Vitro Activity and Comparison with Kanamycin and Gentamicin
Authors: Del Bene Victor E. , Farrar W. Edmund
Published: June 2012

The in vitro activity of the aminoglycoside antibiotic tobramycin was demonstrated by broth dilution and single-disc methods on 50 isolates each of
Staphylococcus aureus, Klebsiella
or
Enterobacter
, indole-positive and -negative
Proteus, Escherichia coli
, and
Pseudomonas aeruginosa
. All organisms were inhibited by 6.25 μg or less of the drug/ml.
Pseudomonas
strains resistant to kanamycin or gentamicin or both were susceptible to tobramycin. Those strains which were inhibited by 6.25 μg of tobramycin/ml by the broth dilution method had zone diameters of 16 mm or more by the single-disc method. Of 313 organisms tested by the disc method, 3 strains were found to be resistant to tobramycin, 73 were resistant to kanamycin, and 18 were resistant to gentamicin. Tobramycin was found to have satisfactory in vitro activity against many clinically important organisms, including strains resistant to gentamicin and kanamycin.
Thiopeptin, a New Feed-Additive Antibiotic: Biological Studies and Field Trials
Authors: Mine K. , Miyairi N. , Takano N. , Mori S. , Watanabe N.
Published: June 2012

Thiopeptin is a new antibiotic, produced by
Streptomyces tateyamensis
and developed solely for animal use as a feed additive. The antibiotic content in animal tissue and feed was assayed in terms of the antimicrobial activity against
Mycoplasma laidlawii
A. This antibiotic was found to be relatively nontoxic in rats and mice. In chickens, this antibiotic is excreted into feces within 48 hr of administration and is not absorbed in tissue. It is well tolerated in both broilers and swine and is highly stable in animal feed. Thiopeptin-supplemented feed contributes to the improvement of weight gain, feed efficiency in chickens and swine, and the egg performance in layers. Thus, thiopeptin, when used as a feed additive, is quite suitable for supplementing animal nutrition.
Antiviral Action and Cellular Toxicity of Four Thymidine Analogues: 5-Ethyl-, 5-Vinyl-, 5-Propyl-, and 5-Allyl-2′-Deoxyuridine
Authors: Cheng Yung-Chi , Domin Barbara A. , Sharma Ram A. , Bobek Miroslav
Published: June 2012

5-Ethyl-, 5-vinyl-, 5-propyl-, and 5-allyl-2′-deoxyuridine (dUrd) had antiviral activity against herpes simplex type 1 and type 2 grown in HeLa TK
−
cells, in the order 5-vinyl-dUrd, 5-ethyl-dUrd, 5-propyl-dUrd, 5-allyl-dUrd, but they were inactive against a TK
−
mutant of herpes simplex type 1. The antiviral activity of these compounds could be partially reversed by thymidine. Except for 5-vinyl-dUrd, they were not toxic to WI-38 and HeLa TK
−
cells at a concentration of 25 μM. All four analogues inhibited the growth of herpes simplex type 1-transformed HeLa TK
−
cells at a concentration of 1 μM.
Antiviral and Interferon-Inducing Activity of a New Glutarimide Antibiotic, 9-Methylstreptimidone
Authors: Saito Noriyuki , Suzuki Fujio , Sasaki Kenji , Ishida Nakao
Published: June 2012

The antiviral effect of 9-methylstreptimidone (9-MS) was examined in mice infected with mouse-adapted influenza A
2
(H
2
N
2
) virus. Both a single and continuous prophylactic administration of 9-MS protected mice from virus infection, and comparison between the minimal effective and the 50% lethal dose gave a therapeutic index of 60. When the treatment was started after infection, however, no antiviral effect was demonstrated. After a single intraperitoneal administration of 9-MS, a highly potent virus-inhibitory factor was detected in the lungs (10 h later) and the sera (16 h later) of uninfected mice, which was assumed to be an interferon on the basis of the biological characteristics. These results suggest that the protective activity of the antibiotic is due to interferon induction in mice.
Acute Diffuse Interstitial Nephritis Related to Chemotherapy of Tuberculosis
Authors: Stone William J. , Waldron James A. , Dixon John H. , Primm R. Kirby , Horn Robert G.
Published: June 2012

Acute renal insufficiency developed in three patients receiving chemotherapy for tuberculosis. It is proposed that acute diffuse interstitial nephritis related to the drugs was responsible for the renal injury. Recovery of renal function was slow and incomplete. Physicians administering chemotherapy to patients with tuberculosis must be aware of the potential nephrotoxicity of the common treatment regimens.
Absence of Penicillin-Degrading Enzymes in Penicillin-Resistant Strains of
Neisseria gonorrhoeae
Authors: Beebe J. L. , Ligeti P. , Wlodkowski T. J.
Published: June 2012

Penicillin-resistant and -susceptible strains of
Neisseria gonorrhoeae
were evaluated for the presence of enzymes capable of degrading penicillin by incubation of [
14
C]benzylpenicillin with resting-cell suspensions of
N. gonorrhoeae
followed by extraction and chromatography of the labeled antibiotic. No degradative activity was observed.
Pharmacokinetic Parameters of Sisomicin
Authors: Meyers Burt R. , Hirschman Shalom Z. , Yancovitz Stanley , Ribner Bruce
Published: June 2012

Sisomicin in doses of 1 mg/kg was administered intramuscularly to 10 healthy volunteers, and 1 week later the same volunteers received sisomicin at the same dose intravenously. A peak serum concentration of sisomicin of 3.08 μg/ml was obtained 1 h after intramuscular injection, and a peak serum concentration of 7.12 μg/ml was achieved 30 min after a 30-min intravenous infusion. The sisomicin elimination data were analyzed according to a two-compartment model. Pharmacokinetic parameters derived from the intramuscular and intravenous studies were quite similar.
Dual-Action Cephalosporin Utilizing a Novel Therapeutic Principle
Authors: Greenwood D. , O'Grady F.
Published: June 2012

A new cephalosporin is described that overcomes, in a novel way, the general susceptibility of this group of agents to enterobacterial β-lactamases. The new compound carries a substituent that is released on cleavage of the β-lactam ring and then exhibits antibacterial activity in its own right. The possible therapeutic benefits of such an antibiotic are discussed.
Pharmacokinetic Interpretation of Cephradine Levels in Serum After Intravenous and Extravascular Administration in Humans
Authors: Rattie Elisabeth S. , Bernardo Peter D. , Ravin Louis J.
Published: June 2012

Pharmacokinetic parameters were calculated from intravenous data based upon a two-compartment open model. These parameters were subsequently used to determine the absorption rates and bioavailability of cephradine administered intramuscularly and orally. The results indicate that cephradine obeys dose-independent kinetics and that biological availability is complete from all dosage forms.
Substrate Inhibition of Beta-Lactamases, a Method for Predicting Enzymatic Stability of Cephalosporins
Authors: Mahoney David F. , Koppel G. A. , Turner J. R.
Published: June 2012

Selected cephalosporins, including cefamandole, cephaloridine, cephaloglycin, and cefoxitin, were examined for their ability to inhibit the enzymatic activity of and act as substrates for beta-lactamases produced by
Enterobacter cloacae
and
Staphylococcus aureus
. Enzyme inhibition was determined by Michaelis-Menten kinetic measurements and by a spot plate assay using a chromogenic substrate (Glaxo compound 87/312). These two methods provide comparable estimates of kinetic parameters. Inhibition of beta-lactamase, as measured by these two methods, was generally found to correlate with resistance to hydrolysis and is proposed as a preliminary method of assessing susceptibility of cephalosporins to beta-lactamase hydrolysis. Four 7-αOCH
3
, 7-αH cephalosporin analogue pairs were also examined. The presence of the 7-αOCH
3
substituent invariably resulted in reduced susceptibility to enzymatic hydrolysis, regardless of the other C7 substituent. The 7-αOCH
3
compounds were also better inhibitors than were their 7-αH analogues, with the exception that 7-αOCH
3
compounds having C7 adipic acid substituents were less inhibitory to the
S. aureus
enzyme than were the corresponding 7-αH analogues. Response of these two enzymes to 7-αOCH
3
and 7-αH cephalosporins suggests that beta-lactamase hydrolysis of these compounds involves attack at the alpha side of the betalactam ring.
Therapeutic Effects of Ribavirin Given by the Intraperitoneal or Aerosol Route Against Influenza Virus Infections in Mice
Authors: Stephen E. L. , Dominik J. W. , Moe J. B. , Walker J. S.
Published: June 2012

Ribavirin (1-β-
d
-ribofuranosyl-1,2,4-triazole-3-carboxamide) is an effective antiviral agent against type A influenza infection of mice. Therapy was most effective when administered as a small-particle aerosol early in the infection. Treatment was also effective by either the intraperitoneal or aerosol route in mice with histological evidence of pneumonia. Ribavirin increased the percent survival, lowered lung virus titers, and decreased the development of lung pathology when therapy was initiated at 6 h as a small-particle aerosol. There was no evidence of pulmonary toxicity or immunosuppressive effects.
Antibiotic Resistance of Bacteria in Water Containing Ornamental Fishes
Authors: Trust T. J. , Whitby J. L.
Published: June 2012

Water containing ornamental fishes was found to frequently contain countable numbers of bacteria that were resistant to one or more antibiotic or chemotherapeutic agents. The multidrug-resistant strains most commonly isolated were lactose-fermenting
Citrobacter freundii
. The overall resistance of these aquaria strains was greater than the previously described resistance of clinical isolates of
C. freundii
. Although the strains examined appeared to lack R-factors, this pool of resistant bacteria may have public health implications.
Kinetics of the Actions of Tetracyclines on
Escherichia coli
as Studied by Microcalorimetry
Authors: Mårdh Per-Anders , Ripa Torvald , Andersson Karl-Erik , Wadsö Ingemar
Published: June 2012

Microcalorimetry was used to study the kinetics of the actions of various tetracyclines on a strain of
Escherichia coli
. Differences in the capacity to suppress the metabolism of this bacterium were observed. When the antibiotic was present from the start of the experiment, a heat production of 2.0 μW/ml was registered after 12.5 h using minocycline; the corresponding figures for doxycycline, oxytetracycline, and tetracycline were 7.3, 6.6, and 4.5 h, respectively. In these experiments, equal concentrations, i.e., half the minimum inhibitory concentration (MIC), of each drug were used. The MIC for all the tetracyclines tested, determined by the broth dilution technique, was 0.8 μg/ml. In other experiments, the antibiotic (concentration, 1.6 μg/ml = 2× MIC) was introduced into the growth vessel during the logarithmic growth phase of the organism. The extent and duration of the inhibitory effect on the metabolism, as judged from the decrease in heat production, varied with the different tetracyclines. Immediately after introduction, minocycline, doxycycline, oxytetracycline, and tetracycline decreased the heat production in decreasing order of potency. With tetracycline, the heat production rose after about 1 h, and with minocycline it rose after about 9 h. The heat production remained at a low level for at least 19 h when using doxycycline and oxytetracycline. The results indicate that microcalorimetry offers a means for studies of the kinetics of the antibacterial actions of antibiotics and provides information that cannot be obtained by conventional bacteriological techniques. This information may be of use, in conjunction with pharmacokinetic data, in establishing optimum doses and dose intervals in antibiotic therapy.
Effects of Doxycycline in Actively Purging Cholera Patients: a Double-Blind Clinical Trial
Authors: Rahaman M. Mujibur , Majid M. A. , Alam A. K. M. Jamiul , Islam M. Rafiqul
Published: June 2012

In 51 actively purging cholera patients the efficacy of doxycycline, a long-acting tetracycline, was compared with a placebo and tetracycline hydrochloride. Seventeen patients who were given doxycycline at the recommended dose of 2 mg/kg at the beginning of the study, at 12 h, and at the repeated dose once daily purged a mean volume of 5.1 liters of stool and received an average of 5.7 liters of intravenous fluid. Nineteen patients receiving the placebo purged 10.1 liters of stool and received 9.7 liters of fluid. Fifteen patients given tetracycline hydrochloride at 6-h intervals passed 4.8 liters of stool and received 5.5 liters of fluid. The durations of diarrhea calculated in 8-h periods were 3.5, 8.0, and 4.1 h in the respective groups receiving doxycycline, placebo, and tetracycline. The differences between the doxycycline and placebo treatments and the tetracycline and placebo treatments were statistically significant. Those receiving doxycycline became vibrio-free in about 3 days as compared with 2 days for those receiving tetracycline; the group given the placebo were vibrio positive for the duration of their hospitalization. The results show that in the treatment of cholera the administration of doxycycline once daily has effects equal to those when tetracycline is administered at 6-h intervals. This is a distinct advantage because it decreases the demand on nursing personnel in epidemics. Also, doxycycline may be safely administered in cases of suspected renal failure from prolonged shock in cholera.
In Vitro Susceptibility of Gentamicin-Resistant
Enterobacteriaceae
and
Pseudomonas aeruginosa
to Netilmicin and Selected Aminoglycoside Antibiotics
Authors: Meyer Richard D. , Kraus Linda L. , Pasiecznik Karen A.
Published: June 2012

Netilmicin (Sch 20569), a semisynthetic aminoglycoside related to gentamicin C
1a
, was evaluated in vitro in agar dilution testing against 224 different clinical isolates of gentamicin-resistant
Enterobacteriaceae
and
Pseudomonas aeruginosa
in parallel with amikacin, gentamicin, sisomicin, and tobramycin. Netilmicin showed a very high degree of activity against gentamicin-resistant organisms, but amikacin was more active in vitro, particularly against
Providencia stuartii
and
P. aeruginosa
. Sisomicin and tobramycin were consistently less active than either netilmicin or amikacin. Netilmicin was bactericidal in broth testing against
P. aeruginosa
. Netilmicin showed a greater difference between results with agar and broth dilution testing than did amikacin.
In Vitro Comparison of Gentamicin, Tobramycin, Sisomicin, and Netilmicin
Authors: Brown K. N. , Benedictson J. , Swanby S.
Published: June 2012

The antimicrobial activity of gentamicin, tobramycin, sisomicin, and netilmicin (Sch 20569) was compared against 150 strains of organisms. Netilmicin was shown to be the least effective against
Pseudomonas
strains but to have slightly better activity against
Staphylococcus aureus
and
Escherichia coli
than the other agents. The effect of calcium and magnesium in enhancing the differences in activity of these aminoglycosides against
Pseudomonas
strains was also demonstrated.
New Medium for In Vitro Susceptibility Studies with Amphotericin B
Authors: Utz C. J. , White S. , Shadomy S.
Published: June 2012

Antibiotic medium 20 FDA and antibiotic medium 3 FDA were compared to determine if antibiotic medium 3 would be suitable for in vitro susceptibility testing with amphotericin B.
Biological Activity of Netilmicin, a Broad-Spectrum Semisynthetic Aminoglycoside Antibiotic
Authors: Miller George H. , Arcieri George , Weinstein Marvin J. , Waitz J. Allan
Published: June 2012

Netilmicin (Sch 20569) is a new broad-spectrum semisynthetic aminoglycoside derived from sisomicin. Netilmicin was compared to gentamicin, tobramycin, and amikacin in a variety of in vitro test systems as well as in mouse protection tests. Netilmicin was found to be similar in activity to gentamicin against aminoglycoside-susceptible strains in both in vitro and in vivo tests. Netilmicin was also active against many aminoglycoside-resistant strains of gram-negative bacteria, particularly those known to possess adenylating enzymes (ANT 2′) or those with a similar resistance pattern. Netilmicin was found to be markedly less toxic than gentamicin in chronic studies in cats, although gentamicin appeared less toxic in acute toxicity tests in mice. The concentrations of netilmicin and gentamicin in serum were compared in dogs after intramuscular dosing, and the pharmacokinetics including peak concentrations in serum were found to be similar.
Reevaluation of the Disk Diffusion Method for Sulfonamide Susceptibility Testing of
Neisseria meningitidis
Authors: Hammerberg Susan , Marks Melvin I. , Weinmaster Gerry
Published: June 2012

Lack of correlation between quantitative minimal inhibitory concentration (MIC) determinations and disk diffusion susceptibility tests in our laboratory prompted a study to reevaluate the use of the disk diffusion test for sulfonamide susceptibility testing of
Neisseria meningitidis
. One hundred and sixty-three recent clinical isolates of
N. meningitidis
were examined for sulfonamide susceptibility by the agar dilution and disk diffusion methods. Optimal inocula for each of the tests were determined, and thereafter all disk diffusion tests were compared with quantitative MICs as determined by the agar dilution method using sulfadiazine and an inoculum of 10
6
colony-forming units (CFU)/ml. The clearest and most reproducible zone diameters were obtained with a 10
7
-CFU/ml inoculum in the disk diffusion test. There was complete correlation between the disk zone diameters for 300-μg disks of sulfadiazine and sulfathiazole and the agar dilution test MICs. All isolates with a zone diameter of <20 mm were resistant to sulfadiazine, whereas those with zone diameters of ≥30 mm were susceptible. False susceptible and false resistant readings were obtained with 300-μg sulfisoxazole disks. These data suggest that inocula and type of sulfonamide are critical factors in the disk diffusion test for meningococcal susceptibility testing. Sulfonamide disks are not interchangeable for susceptibility testing of meningococci.
In Vitro Activity of Gentamicin, Amikacin, and Netilmicin Alone and in Combination with Carbenicillin Against
Serratia marcescens
Authors: Pogwizd Steven M. , Lerner Stephen A.
Published: June 2012

The inhibitory and bactericidal effects of gentamicin, amikacin, netilmicin (Sch 20569), and carbenicillin were tested against 55 clinical isolates of
Serratia marcescens
that had been subtyped into 26 strains by biotyping and serotyping. Three major patterns of resistance to gentamicin, netilmicin, and carbenicillin were recognized among these isolates. (i) Most of the 27 isolates that were susceptible to gentamicin (minimal bactericidal concentration [MBC] ≤6.25 μg/ml) were susceptible to carbenicillin (MBC ≤125 μg/ml) and resistant to netilmicin (MBC ≥12.5 μg/ml). (ii) Most of the 11 isolates with moderate resistance to gentamicin (MBC of 12.5 to 25 μg/ml) were also susceptible to carbenicillin and resistant to netilmicin. (iii) The 17 isolates with high-level resistance to gentamicin (MBC ≥ 50 μg/ml) were all highly resistant to carbenicillin (MBC ≥8,000 μg/ml) but susceptible to netilmicin (MBC ≤6.25 μg/ml). The susceptibility to amikacin was unpredictable among these groups of isolates but, overall, 80% of the isolates were killed by 25 μg of amikacin/ml, which is within the range of peak serum concentrations used therapeutically. Clinically attainable subinhibitory concentrations of carbenicillin enhanced the activity of the three aminoglycosides against all isolates with MBCs of carbenicillin ≤2,000 μg/ml. The 17 isolates with high-level resistance to carbenicillin and gentamicin, as well as the four isolates with high-level resistance to carbenicillin but not to gentamicin, were not susceptible to such enhancement of aminoglycoside activity by carbenicillin.
Effect of Clindamycin on Aminoglycoside Activity in a Murine Model of Invasive
Escherichia coli
Infection
Authors: Ekwo Edem , Peter Georges
Published: June 2012

Previous studies have demonstrated that the early in vitro bactericidal activity of gentamicin and amikacin is inhibited by clindamycin. To investigate the possible clinical implications of these findings, the effect of clindamycin in combination with gentamicin or amikacin was compared with that of the aminoglycoside alone in the treatment of normal and neutropenic mice with
Escherichia coli
peritonitis and bacteremia. Mice treated with saline or clindamycin alone experienced rapid multiplication of bacteria in the peritoneal cavity, bacteremia, and subsequent death. Gentamicin or amikacin given 2 h after
E. coli
inoculation significantly reduced the mortality and peritoneal bacterial counts in normal and neutropenic mice in comparison with untreated controls. Prior or simultaneous administration of clindamycin with either aminoglycoside did not inhibit survival or bacterial clearance from the peritoneum. The only clindamycin effect was slight enhancement of survival of neutropenic mice treated with multiple doses of amikacin and clindamycin in comparison to those treated with amikacin alone.
Cephalosporin and Aminoglycoside Concentrations in Peritoneal Capsular Fluid in Rabbits
Authors: Gerding Dale N. , Hall Wendell H. , Schierl Elizabeth A. , Manion Robert E.
Published: June 2012

To study the penetration of antibiotics into peritoneal tissue fluid, a subcutaneous tissue capsule model was modified by implanting multiple, perforated spherical capsules in the peritoneal cavity of rabbits. Capsules became vascularized, encased in connective tissue, and filled with fluid having a mean protein concentration of 3.6 g/100 ml. Capsular fluid was obtained by percutaneous needle aspiration and assayed for antibiotic by the disk plate bioassay technique. Cephalosporins were administered intramuscularly at a dose of 30 mg/kg. Mean peak concentrations of cephaloridine and cefazolin were significantly higher than cephalothin and cephapirin in capsular fluids, but the percent penetration (ratio of capsular mean peak to serum mean peak) ranged from 8.7 to 16.9% and was not significantly different among the cephalosporins. At 24 h the capsular concentration of cefazolin was significantly greater than for the other cephalosporins (
P
< 0.001). Lower rabbit serum protein binding observed at high in vivo concentrations may have enabled cefazolin to penetrate capsular fluid, but in vitro protein binding studies did not confirm a decrease in serum protein binding at high concentrations within the clinical range. Kanamycin and amikacin showed comparable capsular fluid peak concentrations as did gentamicin and tobramycin. The percent penetration ranged from 15.2 to 34.5% for the aminoglycosides. The only statistical difference was that amikacin penetration was significantly higher than that for tobramycin. Mean capsular concentrations of amikacin, cefazolin, and cephaloridine compared most favorably with the minimum inhibitory concentration of gram-negative bacilli at the dosages used in this study.
Pharmacokinetics of Amoxicillin: Dose Dependence After Intravenous, Oral, and Intramuscular Administration
Authors: Spyker Daniel A. , Rugloski Raymond J. , Vann Robert L. , O'Brien William M.
Published: June 2012

Amoxicillin was studied in normal subjects after intravenous, oral, and intramuscular administration of 250-, 500-, and 1,000-mg doses. Serum drug levels were analyzed using a two-compartment open model, as well as area under the curve (AUC) and urinary recovery. The variations of these pharmacokinetic parameters were then examined using the three-way analysis of variance and linear regression equations. These results confirmed nearly complete oral absorption: AUC was 93% of intravenous absorption, and urinary recovery was 86%. The intramuscular administration of amoxicillin results in complete and reliable absorption with peak drug levels, AUCs, and urinary recovery equivalent to oral dosage. The absorption of lyophilized amoxicillin after intramuscular injection resulted in an AUC that was 92% of intravenous absorption and urinary recovery of 91%. The peak serum levels, time to peak, and other pharmacokinetic parameters for intramuscular injection were nearly identical to those for oral administration. Kinetics of both intramuscular and oral administration exhibited dose-dependent absorption (absorption rate constant, 1.3/h for 250 mg and 0.7/h for 1,000 mg). This resulted in relatively later and lower peak serum levels for increasing dose. Total absorption, however, showed no dose dependence, as indicated by urinary recovery and AUC, which changed by less than 10%.
Interferon Induction in Cynomolgus and Rhesus Monkeys After Repeated Doses of a Modified Polyriboinosinic-Polyribocytidylic Acid Complex
Authors: Sammons M. L. , Stephen E. L. , Levy H. B. , Baron S. , Hilmas D. E.
Published: June 2012

Serum interferon activity was determined in 12 cynomolgus and 12 rhesus monkeys injected intravenously once daily for 10 days with from 0.1 to 6.0 mg of a stabilized polyriboinosinic acid · polyribocytidylic acid complex per kg, composed of polyriboinosinic acid · polyribocytidylic acid, poly-1-lysine, and carboxymethylcellulose [poly(ICLC)]. Interferon activity was detected 2 h after the first injection, with maximum activity occurring 8 h after the second injection. A period of hyporesponsiveness occurred after the third injection of poly(ICLC) in all monkeys and lasted until the sixth injection in the rhesus monkeys, when interferon activity again became more elevated. The delayed rebound was not as apparent in cynomolgus monkeys. Rhesus monkeys injected with 6 mg/kg did not exhibit serious side effects.
Inactivation of Lipid-Containing Viruses by Long-Chain Alcohols
Authors: Snipes Wallace , Person Stanley , Keller Gregory , Taylor William , Keith Alec
Published: June 2012

This report describes the inactivation of lipid-containing viruses by several long-chain alcohols. A striking peak in antiviral activity was found for saturated alcohols having chain lengths from 10 to 14 carbons. Viruses having different membrane structure showed different susceptibilities to alcohols having different chain lengths and structural features. Decanol, dodecanol, and tetradecanol readily inactivated herpes simplex virus and the enveloped bacterial virus φ6. The lipid-containing virus PM2 was susceptible to decanol and dodecanol but comparatively unsusceptible to tetradecanol. The branched-chain alcohol phytol, a naturally occurring component of chlorophyll, was active against φ6 and herpes simplex virus but not against PM2. Polyoma virus and the bacteriophage φ23-1-a, which do not contain lipids, were not susceptible to inactivation by any of the alcohols tested. Experiments were also carried out to determine the effects of these compounds on cells. At 0.5 mM, decanol lysed human embryonic lung cells, erythrocytes, and the bacterial hosts for φ6 and PM2. Dodecanol, tetradecanol, and phytol at this concentration were less damaging to cells. At 0.05 mM, none of the alcohols caused observable cytopathic effects on human embryonic lung cells, although several of the alcohols at this concentration were active against herpes simplex virus. Our findings suggest that dodecanol, tetradecanol, and phytol may warrant further studies as potential antiviral agents, particularly for topical application to virus-infected areas of the skin.
Drug Resistance and R Plasmids in
Salmonella typhi
Isolated in Korea
Authors: Chun Doki , Seol Sung Yong , Cho Dong Taek , Tak Ryunbin
Published: June 2012

A total of 949 strains of
Salmonella typhi
isolated in Korea from 1968 to 1975 were tested for drug resistance and distribution of R plasmids. Resistance was mostly restricted to streptomycin (SM) and sulfisomidine (SA), singly or in combination, at a low degree. A small number of strains (1.5%) were resistant to four or more drugs: chloramphenicol (CM), tetracycline (TC), SM, SA, ampicillin (AP), and kanamycin (KM). No strain was resistant to nalidixic acid or to a 1:20 mixture of trimethoprim and sulfamethoxazole. Nor was there any strain singly resistant to CM, TC, AP, or KM. Transfer experiments of multiple-drug resistance to
Escherichia coli
ML1410 showed that all the strains resistant to four or more drugs carried R plasmids, whereas those weakly resistant to three or less drugs did not. The quadruply resistant strains carried one R plasmid determining CM, TC, SM, and SA resistance, and sextuply resistant ones carried two plasmids, one determining CM, TC, SM, and SA resistance and the other determining AP and KM resistance. One strain carrying a plasmid determining AP and KM resistance was also found. The transfer frequency of CM, TC, SM, and SA resistance was much higher than that of AP and KM resistance. The resistance of
S. typhi
was more efficiently transferred to
E. coli
at 25°C than at 37°C.
In Vitro Activity of Ticarcillin Against Anaerobic Bacteria Compared with That of Carbenicillin and Penicillin
Authors: Roy Ira , Bach Vinh , Thadepalli Haragopal
Published: June 2012

A total of 334 clinical anaerobic isolates were tested in an anaerobic glove box by the agar dilution technique for susceptibility to clinically achievable levels of ticarcillin, carbenicillin, and penicillin. Thirty-two micrograms or less of penicillin per milliliter inhibited 91% of all strains, whereas 100 μg of carbenicillin and ticarcillin per ml inhibited 95 and 98%, respectively. A total of 82% (85 strains) of
Bacteroides
were inhibited by penicillin, and 93 and 96% were inhibited by carbenicillin and ticarcillin, respectively. Thirteen (24%) of 55 strains of
Bacteroides fragilis
tested were resistant to 32 μg of penicillin per ml, and 6 (11%) and 3 (5%) were resistant to 100 μg of carbenicillin and ticarcillin per ml, respectively. Within the therapeutic range, ticarcillin was the most effective of the three penicillins tested against
B. fragilis
subsp.
fragilis
.
Relationship Between the Physicochemical Nature of Human Interferon, the Cell Induced, and the Inducing Agent
Authors: Cesario Thomas C. , Schryer Patricia J. , Tilles Jeremiah G.
Published: June 2012

To determine the basis for differences in interferons previously noted by others, we prepared five types of human interferon, namely interferon induced in muscle skin fibroblasts using complexed polyinosinic:polycytidylic acid (IC) and Newcastle disease virus (NDV), and interferon induced in leukocytes using IC, NDV, and phytohemagglutinin. We determined the molecular weight, isoelectric point, inactivation rate at 56°C and structural activity relationships for each interferon. Significant differences between these interferons were found, many of which seem related to the cell induced rather than the inducer. We believe these findings have important pharmacological implications for the use of interferon in man.
Cefadroxil, a New Broad-Spectrum Cephalosporin
Authors: Buck R. E. , Price K. E.
Published: June 2012

Cefadroxil is a new semisynthetic cephalosporin with a broad antibacterial spectrum and a high chemotherapeutic potential when administered orally. The inhibitory activity of this compound was similar to that of cephalexin and cephradine when tested against 602 clinical isolates on Mueller-Hinton medium. In the oral treatment of experimental infections of mice, cefadroxil was more effective than cephalexin against
Streptococcus pyogenes
, and comparably effective against
Streptococcus pneumoniae, Staphylococcus aureus
, and several gram-negative species. Administered orally to mice, at doses ranging from 25 to 100 mg/kg, cefadroxil attained peak concentrations in the blood similar to those of cephalexin. At a dose of 200 mg/kg, however, higher peak levels were noted with cefadroxil than with cephalexin. In regard to other properties which were investigated, the behavior of cefadroxil compared favorably to that of cephalexin.
Gardimycin, a New Antibiotic Inhibiting Peptidoglycan Synthesis
Authors: Somma Sergio , Merati Wilma , Parenti Francesco
Published: June 2012

Gardimycin, a new antibiotic, at 100 μg/ml, specifically inhibited cell wall synthesis and induced accumulation of uridine 5′-diphosphate-
N
-acetylmur-amylpentapeptide in whole cells of
Bacillus subtilis
. The antibiotic was active in a particulate enzyme preparation from
Bacillus stearothermophilus:
60 μg/ml caused 50%, and 200μg/ml caused 100%, inhibition of peptidoglycan synthesis. Suppression of peptidoglycan synthesis was accompanied by parallel accumulation of the lipid intermediate. This mechanism of action is discussed in comparison with those of other antibiotics that are known to inhibit bacterial cell wall biosynthesis.
In Vivo Effects of Josamycin, Erythromycin, and Placebo Therapy on Nasal Carriage of
Staphylococcus aureus
Authors: Wilson Samuel Z. , Martin R. Russell , Putman Margaret
Published: June 2012

Healthy nasal carriers of
Staphylococcus aureus
were randomly assigned to one of three treatment regimens: josamycin (1.5 g/day), erythromycin stearate (1.0 g/day), or placebo, each administered orally for 7 days. Quantitative nasal cultures were obtained from each subject at intervals before, during, and after treatment. All 25 placebo-treated subjects had positive nasal cultures for
S. aureus
at all culture intervals. Both josamycin and erythromycin were equally effective in reducing the carrier rates and in decreasing the total numbers of
S. aureus
isolated from subjects with positive cultures during treatment. No increase in in vitro antibiotic resistance was detected in isolates obtained after therapy. Both antibiotics were well tolerated, and toxicity was not encountered with either drug.
Comparison of In Vitro Activity of Cephalexin, Cephradine, and Cefaclor
Authors: Bill Nancy J. , Washington John A.
Published: June 2012

Inhibitory activity of cephalexin, cephradine, and cefaclor was compared by the WHO-ICS agar dilution technique. Cefaclor was substantially more active against staphylococci, streptococci, gonococci, meningococci,
Haemophilus, Escherichia coli, Klebsiella pneumoniae, Citrobacter diversus, Proteus mirabilis
, salmonellae, and shigellae than was cephalexin, which in turn was more active than cephradine. Cefaclor appeared to be less resistant to staphylococcal penicillinase than did the other two agents. None of these cephalosporins was active against
Enterobacter, Serratia
, indole-positive
Proteeae, Pseudomonas
, or
Bacteroides fragilis
.
Cytochemical and Biochemical Studies of Yeasts After In Vitro Exposure to Miconazole
Authors: De Nollin Sonja , Van Belle H. , Goossens F. , Thone F. , Borgers M.
Published: June 2012

Yeast cells exposed to different doses of the antimycotic agent miconazole revealed important cytochemical changes in the topographic distribution of the phosphatases. A strong effect was observed on the behavior of oxidative and peroxidative enzymes. Decreased cytochrome
c
oxidase and peroxidase activity and increased catalase activity were seen after treatment with a fungistatic dose of miconazole, whereas a complete disappearance of these enzymes was observed after treatment with a minimal fungicidal dose of miconazole. This was in complete agreement with the quantitative biochemical data. A hypothesis is advanced concerning the possible involvement of peroxidase and catalase in the mechanism of action of this drug.
Plasmid-Mediated Beta-Lactamase Production in
Neisseria gonorrhoeae
Authors: Elwell Lynn P. , Roberts Marilyn , Mayer Leonard W. , Falkow Stanley
Published: June 2012

Several β-lactamase-producing, penicillin-resistant strains of
Neisseria gonorrhoeae
were examined for R plasmids. Penicillin-resistant strains isolated from men returning from the Far East and their contacts contained a 4.4 × 10
6
-dalton plasmid in common. Transformation studies and the isolation of a spontaneous penicillin-susceptible segregant showed that the structural gene for β-lactamase was part of the 4.4 × 10
6
-dalton plasmid. An additional penicillin-resistant gonococcal strain isolated in London was found to harbor a 3.2 × 10
6
-dalton R plasmid. Deoxyribonucleic acid (DNA)-DNA duplex studies revealed that the penicillin-resistant gonococcal isolates contained a significant portion (about 40%) of the transposable DNA sequence, TnA, which includes the β-lactamase gene commonly found on R plasmids of the
Enterobacteriaceae
and
Haemophilus influenzae
.
Ampicillin-Induced Morphological Alterations of
Haemophilus influenzae
Type b
Authors: Klein Richard D. , Luginbuhl G. H.
Published: June 2012

Inhibitory levels of ampicillin induced filamentation of growing
Haemophilus influenzae
ATCC 19418 within 30 min. Filaments became swollen and interrupted by regular periodic saccular outpouchings along the major axis. The degree of filamentation was dependent upon ampicillin concentration and time.
Stimulation of Interferon Production in Mice and in Mouse Spleen Leukocytes by Analogues of BL-20803
Authors: Siminoff Paul , Crenshaw R. R.
Published: June 2012

Various structural analogues of the interferon inducer BL-20803 exhibited close agreement between ability to stimulate interferon production in the intact mouse and in cultures of spleen adherent leukocytes.
Measurement of Polyene Antibiotic-Mediated Erythrocyte Damage by Release of Hemoglobin and Radioactive Chromium
Authors: Siegel E. B.
Published: June 2012

Polyene antifungal antibiotics produce various degrees of membrane damage in sheep erythrocytes in vitro. Mediocidin, filipin, amphotericin B, and candicidin were found to result in greater damage than nystatin, pimaricin, and amphotericin B methyl ester. The degree of sensitivity of the cells varied by 100-fold for mediocidin verus amphotericin B methyl ester as measured by curves of hemoglobin release versus drug concentration. In erythrocytes prelabeled with radioactive chromium, release of the isotope through polyene-damaged cell membranes was found to occur at lower drug concentrations than measurable hemoglobin release, and the percentage of isotope released at the highest drug dose was consistently greater than the percentage of hemoglobin released. Thus, the isotope assay is a more sensitive indicator of polyene-induced membrane damage in the test system. These significant differences in release of molecules through polyene-induced membrane lesions indicate the complex nature of the binding and further interactions of this class of drugs with the plasma membrane.
Chemotherapy of Genital Herpes Simplex Virus Type 2 Infections of Female Hamsters
Authors: Renis Harold E.
Published: June 2012

The antiviral activity of 1-β-
d
-arabinofuranosylcytosine (ara-C, cytarabine, Cytosar), 5-iodo-2′-deoxyuridine (IdUrd), 9-β-
d
-arabinofuranosyladenine (ara-A), and disodium phosphonoacetate (PAA) have been compared in herpes simplex virus type 2 (HSV-2)-infected primary rabbit kidney cells and in female hamsters with genital HSV-2 infection. In vitro, ara-C and IdUrd were more active than ara-A, and PAA was least active. In female hamsters with genital HSV-2 infection, intravaginal treatment with PAA or ara-A was more effective than either ara-C or IdUrd. PAA was more active than ara-A when treatment was initiated early (1 h) after infection. The activity of PAA was greatly reduced if initiation of treatment was delayed for 24 h. Both PAA and ara-A reduced the virus titers of the vagina and protected hamsters from death when the drugs were given by either the intravaginal or subcutaneous route, with intravaginal treatment being more effective.
Cefoxitin Resistance to Beta-Lactamase: a Major Factor for Susceptibility of
Bacteroides fragilis
to the Antibiotic
Authors: Darland Gary , Birnbaum Jerome
Published: June 2012

Toluene-treated cell suspensions of
Bacteroides fragilis
were used to screen clinical isolates for the production of β-lactamase. Approximately one-third of the isolates possessed considerable cephalosporinase activity. A significant correlation was found between β-lactamase production and resistance to cephalosporin antibiotics. Several isolates were resistant to cefuroxime and cefamandole and produced enzymes capable of hydrolyzing these antibiotics. However, none of the 79 strains tested could hydrolyze the cephamycin derivative, cefoxitin. A large percentage (>90%) of the strains were susceptible to cefoxitin. Therefore, resistance to lactamase hydrolysis is a major factor for the effectiveness of cefoxitin against
B. fragilis
. Detailed studies of four isolates suggest that two different enzymes may be produced. Both are cephalosporinases but differ with regard to cellular distribution and substrate specificity. Cefoxitin is not a substrate for either enzyme, but it is an excellent competitive inhibitor (

K
i

≈ 0.1 μM).
Amphotericin B and Filipin Effects on L and HeLa Cells: Dose Response
Authors: Kotler-Brajtburg Janina , Medoff Gerald , Schlessinger David , Kobayashi George S.
Published: June 2012

Amphotericin B (AmB) and filipin effects on L and HeLa cells were compared by monitoring drug-induced potassium leakage from cells, changes in radioactive uridine incorporation into cellular ribonucleic acid, protein leakage from cells, and cell viability. L cells were much more susceptible to both AmB and filipin than were HeLa cells, but the overall dose response was similar. For AmB, the various effects were easily separable. Potassium leakage occurred at the lowest concentrations of AmB and was reversible. Inhibition of uridine incorporation and loss of viability occurred at intermediate levels, and protein loss occurred at higher levels. In contrast, filipin was much more potent; its effects on potassium leakage were only minimally reversible, and the separation of the permeabilizing effects from complete cell lysis was possible only over a limited concentration range and for a short time.
Renal Pharmacology of Netilmicin
Authors: Chiu Peter J. S. , Miller George H. , Brown Arthur D. , Long James F. , Waitz J. Allan
Published: June 2012

Netilmicin (Sch 20569), a new semisynthetic aminoglycoside, was studied for its effects on kidney function and mechanisms by which it is handled by the kidneys. Measurements of glomerular filtration rate (GFR) and urinalysis in chronic rat studies indicated that the nephrotoxicity of netilmicin was remarkably less than that of gentamicin. Gentamicin caused a dose-related reduction in GFR in association with glucosuria and elevated fractional excretion of K
+
. By contrast, high doses of netilmicin produced only slight reduction in GFR with increased fractional excretion of K
+
but without glucosuria. In separate experiments, rats were shown to excrete 71 to 90% of netilmicin or gentamicin in 24 h after daily intramuscular administration of doses of 20 or 40 mg/kg for 4 days. In acute experiments on anesthetized dogs, GFR and renal plasma flow were unaffected at serum levels of 11.0 ± 0.6 μg/ml maintained by constant infusion of netilmicin for 5 h. The renal clearance of netilmicin was significantly correlated with GFR. The urinary output of netilmicin was 80.0 ± 4.2% of the infusion rate and was independent of urine flow over the range of 0.04 to 0.33 ml/kg per min. Preferential accumulation of netilmicin occurred in the renal cortex; the cortex–serum and medulla–serum ratios were 9.9 ± 1.2 and 4.2 ± 0.6, respectively. In addition, the extraction ratio of netilmicin, which was lower than that of inulin, suggested that netilmicin reabsorption occurs in the proximal tubule and results in cortical accumulation. It is concluded that netilmicin, like gentamicin, is excreted by the dog kidney by glomerular filtration plus limited reabsorption. However, the new drug is characterized by low intrinsic nephrotoxicity in rats.
Extreme Sensitivity of Staphylococcal Enterotoxin B and C Production to Inhibition by Cerulenin
Authors: Altenbern Robert A.
Published: June 2012

Production of staphylococcal enterotoxins B and C was completely inhibited by concentrations of cerulenin (4 μg/ml and 2 μg/ml, respectively) that did not affect either growth rate or final growth density. Type A toxin formation was not similarly inhibited.