bluuebunny/crossref_metadata_2025 huggingface dataset:
5-Fluorocytosine Resistance in
Cryptococcus neoformans
Authors: Block Edward R. , Jennings Anne E. , Bennett John E.
Published: June 2012

Isolates of
Cryptococcus neoformans
from six patients were obtained before and after unsuccessful therapy with 5-fluorocytosine (5-FC). Post-therapy isolates exhibited massive and stable 5-FC resistance. The frequency of drug-resistant mutants in susceptible isolates of
C. neoformans
was <0.001% (70.4 ± 17.9 per 10
7
cryptococci), whereas mutant frequencies in resistant isolates approached 100%. Non-drug-induced, spontaneously appearing 5-FC resistant mutants were documented in four susceptible isolates of
C. neoformans
by use of the statistical method of fluctuation analysis. Mutation rates on these same four isolates ranged from 1.2 × 10
−7
to 4.8 × 10
−7
. Total intracellular uptake and incorporation of cytosine-
5
-
3
H
(CyH
3
) and 5-fluorocytosine-
2
-
14
C
(5-FC
14
) into a trichloroacetic acid-insoluble fraction were markedly reduced in six isolates with in vivo-acquired resistance when compared with susceptible pretreatment strains from the same patients. Five of these six isolates also had acquired massive resistance to 5-fluorouracil (5-FU), suggesting that a mutation in the uridine-5′-monophosphate pyrophosphorylase was responsible for drug resistance. The sixth isolate, which remained susceptible to 5-FU, appeared to have a defect in a cytosine-specific permease accounting for 5-FC resistance. A single isolate with in vitro-acquired 5-FC and 5-FU resistance had no reduction in uptake or incorporation of CyH
3
or 5-FC
14
. The mechanism of resistance in this isolate is discussed.
BL-20803, a New, Low-Molecular-Weight Interferon Inducer
Authors: Siminoff Paul , Bernard Anthony M. , Hursky Valentina S. , Price Kenneth E.
Published: June 2012

BL-20803 induced interferon in mice when administered via oral or parenteral routes. During multiple dosing with the drug at 48-h intervals, animals exhibited a hyporesponsive state to the third treatment. Inhibition of vaccinia virus infection was correlated with interferon induction.
Scanning Electron Microscopy of the H37Ra Strain of
Mycobacterium tuberculosis
Exposed to Isoniazid
Authors: Takayama Kuni , Wang Lynn , Merkal Richard S.
Published: June 2012

The morphology of cells of the H37Ra strain of
Mycobacterium tuberculosis
exposed to 0.5 μg of isonicotinic acid hydrazide (isoniazid) per ml was examined by scanning electron microscopy (SEM). Cells that were exposed to isoniazid for 3 h showed no detectable change, whereas cells exposed to the drug for 24 h exhibited diverse morphological features. From our examination of these SEM pictures, we have reconstructed the probable sequence of morphological changes to be as follows: (i) the wrinkling of the cell surface was ascribed as the earliest observable change, (ii) the cell surface then became very rough and ragged, (iii) eventually the cytoplasmic material was extruded from the cell, (iv) this event produced a collapsed cell, (v) the cells began to fragment, (vi) the fragmented cells then coalesced to form an amorphous mass of cell debris.
Synergism of Vancomycin-Gentamicin and Vancomycin-Streptomycin Against Enterococci
Authors: Watanakunakorn Chatrchai , Bakie Cheryl
Published: June 2012

The in vitro activity of vancomycin and combinations of vancomycin-gentamicin and vancomycin-streptomycin against enterococci was investigated. The minimal inhibitory concentration of vancomycin for 99 of 100 enterococcal strains isolated clinically was 3.12 μg or less/ml. When cultures of eight strains were incubated with vancomycin, regardless of the inoculum size (10
6
, 10
5
, or 10
4
) and concentration of vancomycin (10 or 20 μg/ml), there was no significant reduction in the number of viable enterococci at 6, 24, and 48 h. Gentamicin and streptomycin in concentrations attainable clinically were not effective against enterococci. Vancomycin combined with gentamicin or streptomycin was tested against 41 enterococcal strains. With the combination of vancomycin at 10 μg/ml and gentamicin at 4 μg/ml or vancomycin at 5 μg/ml and gentamicin at 4 μg/ml, synergism was demonstrated against all 41 strains at 6 h. The combination of vancomycin at 10 μg/ml and streptomycin at 10 μg/ml was only synergistic against 25 of 41 strains at 6 h, and only 22 of 41 strains were affected synergistically at 6 h by vancomycin at 5 μg/ml with streptomycin at 10 μg/ml. With few exceptions, the enhanced killing was more pronounced at 24 and 48 h. The combination of vancomycin and gentamicin or vancomycin and streptomycin (where in vitro studies demonstrate synergism) may be a useful alternate therapy in enterococcal endocarditis.
Maridomycin, a New Macrolide Antibiotic: In Vivo Antibacterial Activity of 9-Propionylmaridomycin
Authors: Kondo Masahiro , Ishifuji Kiyoshi , Tsuchiya Kanji , Goto Sachiko , Kuwahara Shogo
Published: June 2012

The in vivo protecting activity of 9-propionylmaridomycin, a derivative of the new macrolide antibiotic, maridomycin, was compared with that of other macrolide antibiotics in mice infected with
Staphylococcus aureus, Streptococcus pyogenes
, and
Diplococcus pneumoniae
. The protective effect was almost similar to that afforded by several known macrolide antibiotics in mice infected intraperitoneally with certain strains of the gram-positive species described above. The skin lesion caused by intradermal challenge of
S. aureus
in mice also responded very effectively to treatment with 9-propionylmaridomycin.
Antimicrobial Susceptibility of
Nocardia
Species
Authors: Lerner Phillip I. , Baum Gerald L.
Published: June 2012

Variations of inoculum, pH, and composition of the agar assay media each influenced the in vitro susceptibility of
Nocardia
organisms (30 strains of
N. asteroides
and 6 strains of
N. brasiliensis
) to one or more antimicrobial agents incorporated in solid agar and incubated at 37 C for 48 h. Among newer antimicrobial agents, doxycycline, minocycline, and 7-halogenated lincomycin analogues exhibited the most consistent in vitro inhibitory activity; among older agents, viomycin, erythromycin, and streptomycin exhibited more selective in vitro inhibitory activity, but against a significant percentage of strains tested.
N. brasiliensis
was conspicuously more susceptible to erythromycin and gentamicin and more resistant to viomycin and capreomycin than was
N. asteroides
. Cycloserine demonstrated no significant in vitro inhibitory activity when assayed in appropriately augmented alanine-free medium. The outstanding feature of this in vitro survey was the marked variation in susceptibility among individual strains of
N. asteroides
, which variation deserves more careful consideration in future clinical or experimental therapeutic trials.
Effect of Temperature on the In Vitro Susceptibility of
Staphylococcus aureus
to Penicillinase-Resistant Penicillins
Authors: Thornsberry Clyde , Caruthers J. Q. , Baker Carolyn N.
Published: June 2012

Heteroresistant (methicillin-resistant) and nonheteroresistant strains of
Staphylococcus aureus
were tested for their susceptibility to penicillinase-resistant penicillins at incubation temperatures of 37, 35, and 30 C. Susceptibilities were determined by agar dilution and by the standard Kirby-Bauer agar diffusion tests. Minimal inhibitory concentrations were higher at 35 and 30 C than at 37 C. Heteroresistance could be detected with the Kirby-Bauer test if the incubation temperature was 30 or 35 C instead of 37 C, when tests were performed against methicillin, oxacillin, or nafcillin, because the resistant organisms grew up to the disks even though the susceptible organisms were inhibited. At 37 C, the resistance was detectable with some strains but not with others. When cloxacillin disks were used, the temperature effect was not seen. The incubation temperature did not affect results with nonheteroresistant strains. Therefore, it is recommended that all Kirby-Bauer tests be incubated at a temperature of 35 C to insure detection of methicillin-resistant
S. aureus
strains. Detection of these strains is of increasing importance because the incidence of infections with these organisms is increasing, particularly in hospitalized patients.
Tobramycin in Bronchial Secretions
Authors: Pennington James E. , Reynolds Herbert Y.
Published: June 2012

The penetration of tobramycin sulfate (nebramycin factor 6) into normal lower respiratory tract secretions was studied in a dog model. After a 1.7 mg/kg intravenous dose of tobramycin, the antibiotic was detected promptly in bronchial secretions, but the peak bronchial secretion concentration was not usually reached until 2 h after injection (mean level 1.15 μg/ml). The maximum tobramycin concentration in bronchial fluids was equal to the mean inhibitory concentrations that have been reported for about 80% of
Pseudomonas
isolates.
Chemotherapeutic Activity of 5-Fluorocytosine and Amphotericin B Against
Candida albicans
in Mice
Authors: Titsworth E. , Grunberg E.
Published: June 2012

The effect of treatment with combinations of the two antifungal agents, 5-fluorocytosine (5-FC) and amphotericin B (AB), against systemic
Candida albicans
infections in mice was investigated. Graded doses of the single substances and of combinations of the drugs were administered daily for 21 days. The 50% curative dose (CD
50
) values were calculated on the basis of the presence or absence of
C. albicans
in cultures prepared from the kidneys of animals that succumbed during the experimental period or were sacrificed at the termination of the experiments. Overall, when graded doses of AB were administered in the presence of a constant, inactive dose of 5-FC (approximately one-half to one-fourth the CD
50
of 5-FC), the CD
50
values for AB were lower than those for amphotericin B alone. Similarly, the CD
50
s for 5-FC were reduced when AB was administered at a constant dose equal to one-half to one-fourth the CD
50
of AB alone. In no instance was there evidence of antagonism.
Pharmacodynamics of Cefazolin in the Presence of Normal and Impaired Renal Function
Authors: Rein Michael F. , Westervelt Frederic B. , Sande Merle A.
Published: June 2012

The excretion of cefazolin, a new cephalosporin antibiotic, was studied in subjects with normal and impaired renal function. Twelve subjects with creatinine clearances ranging from 0 to 144 ml per min per 1.73 m
2
were given a single 500-mg intramuscular dose of cefazolin. Serum and urine levels were determined at intervals by agar diffusion. Peak serum levels in normals ranged from 44 to 70 μg/ml and occurred 30 to 60 min after injection. The mean serum half-life in normals was 1.6 h, and this was prolonged from 20 to 40% by simultaneous administration of probenecid. The total elimination constant varied linearly with the creatinine clearance in patients with renal impairment. The serum half-life in anephric patients was about 42 h. The fractional clearance of the drug varied directly with the serum level. Peak urine levels ranged from 60 to over 2,000 μg/ml, and more than 90% of the dose was recovered in the urine of normals during the first 24 h. The data suggest that cefazolin is cleared primarily by the glomerulus, with tubular and biliary secretion playing a secondary role.
Immunosuppressive Effect of 6-Mercaptopurine and Mitomycin C
Authors: Majeski James A. , Cole B. Theodore
Published: June 2012

6-Mercaptopurine and mitomycin C were used in combination drug therapy to produce a prolongation of skin allograft survival.
Bactericidal Action of an Antibiotic Produced by
Myxococcus xanthus
Authors: Rosenberg E. , Vaks B. , Zuckerberg A.
Published: June 2012

Myxococcus xanthus
produced an antibiotic during the end of its exponential growth phase which was capable of inhibiting growth of several gram-positive and gram-negative bacteria. The antibiotic was bactericidal to growing cultures only; chloramphenicol inhibited the bactericidal action of the antibiotic. Upon addition of the antibiotic to
Escherichia coli
B, deoxyribonucleic acid and ribonucleic acid as well as turbidity of the culture continued to increase even after the viable count decreased; the culture lysed about 60 min after addition of sufficient concentrations of the antibiotic. Spheroplasts could be prepared if the antibiotic was added to a culture growing in the presence of high concentrations of sucrose and MgSO
4
. Mutants of
M. xanthus
FB which are incapable of fruiting body formation or glycerol-induced myxospore formation also produced the antibiotic. A mutant of
E. coli
resistant to the purified antibiotic was isolated in order to study the role of the antibiotic in the predatory behavior of myxococci.
Pharmacology of Gentamicin in the Biliary Tract of Humans
Authors: Mendelson J. , Portnoy J. , Sigman H.
Published: June 2012

Serum and biliary tract levels of gentamicin were determined in a large series of patients. In only 17.7% of subjects were therapeutic serum levels achieved, even though recommended doses of gentamicin were administered. Therapeutic bile gentamicin levels were reached in only some of the patients with therapeutic serum levels.
Successful Treatment of
Pseudomonas cepacia
Endocarditis with Trimethoprim-Sulfamethoxazole
Authors: Hamilton John , Burch Warner , Grimmett Garfield , Orme Kirby , Brewer David , Frost Richard , Fulkerson Conrad
Published: June 2012

A patient with a history of alcoholism and drug abuse who developed
Pseudomonas cepacia
endocarditis is described. The organism was found to be resistant in vitro to all common antimicrobial agents except chloramphenicol and trimethoprim-sulfamethoxazole. Treatment failed with penicillin and streptomycin and later with chloramphenicol. Orally administered trimethoprim-sulfamethoxazole, however, resulted in sterilization of the patient's blood and aortic valve which was resected 27 days after the start of therapy. A 6-week course of therapy was completed and, to date (6 months after treatment), there has been no recurrence.
Synergism of Carbenicillin and Gentamicin Against Enterococci
Authors: Libke Robert D. , Regamey Claude , Clarke John T. , Kirby William M. M.
Published: June 2012

Carbenicillin and gentamicin were tested for synergism against 25 strains of enterococci by two different methods. Killing curves were determined by doing serial colony counts of broth cultures containing the antibiotics separately and in combination. The combination was synergistic for all 25 strains with 75 and 4 μg of carbenicillin and gentamicin per ml, respectively. Reducing the concentrations to 50 and 3 μg of the antibiotics per ml with four strains significantly reduced the rate of killing of the combination. Synergism was also studied by constructing isobolograms, by using the standard two-dimensional broth dilution checker-board technique, and by measuring the end points both for minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs). Synergism was present for all 25 strains when bactericidal end points (MBCs) were evaluated, but was present for only 7 of the 25 strains when MICs were used to construct isobolograms. The time and effort involved were roughly the same for killing curves and for isobolograms, and it was concluded that neither had a distinct advantage over the other.
Silver Sulfadiazine: In Vitro Antibacterial Activity
Authors: Carr Howard S. , Wlodkowski Theodore J. , Rosenkranz Herbert S.
Published: June 2012

Isolates (657) representing 22 bacterial species were tested for susceptibility to silver sulfadiazine. All of the strains tested were inhibited by concentration levels of the drug which are easily achieved topically. It is suggested that silver sulfadiazine may be useful as a broad-spectrum antimicrobial substance for the prevention and treatment of infections of burns and wounds.
Double-Blind Comparison of Carbenicillin Indanyl Sodium, Ampicillin, and Cephalexin in Treatment of Urinary Tract Infection
Authors: Ries Kristen M. , Cobbs C. Glenn , Gillenwater Jay Y. , Levison Matthew E. , Mandell Gerald L. , Sande Merle A. , Kaye Donald
Published: June 2012

Carbenicillin indanyl sodium, ampicillin, or cephalexin was administered orally to 61 patients with urinary tract infections. Assignment of drug was made by a computer-generated, randomized plan in a double-blind fashion. The rates of cure 4 weeks after therapy were 50, 42, and 50% for patients treated with carbenicillin, ampicillin, and cephalexin, respectively. Failure of therapy was correlated with chronicity of infection and sensitivity of the microorganism to the antibiotic used. Thirty-nine percent of the patients developed side effects, but there were no significant differences in side effects among the three antibiotics. This double-blind study demonstrates that carbenicillin indanyl sodium is as effective as ampicillin and cephalexin in treatment of urinary tract infections.
Binding of Gentamicin and Other Aminoglycoside Antibiotics to Mycelium of Various Actinomycetes
Authors: Reiblein W. J. , Watkins P. D. , Wagman G. H.
Published: June 2012

Gentamicin, an aminoglycoside antibiotic, occurs both free in the fermentation filtrate and bound to the mycelium of the producing organism,
Micromonospora purpurea
. The bound gentamicin, which represents the major portion of the total quantity present in the fermentation broth, was released after exposure to acid, alkali, or sonic disruption. Washing the mycelium with distilled water, heat treatment, and the addition of sodium chloride to the fermentation medium were not effective methods for releasing bound gentamicin. Gentamicin and other aminoglycoside antibiotics were effectively adsorbed from neutral aqueous solutions by the acid-extracted mycelium of
M. purpurea
. In addition, the acid-extracted mycelium of actinomycetes other than
M. purpurea
were shown to be able to adsorb gentamicin from solution.
Pseudomonas
Resistance Due to Inactivated Susceptibility Disks
Authors: Griffith Lewis J.
Published: June 2012

The deterioration of carbenicillin is similar to that of other penicillins. Susceptibility test results, by using disks which have been exposed to humidity, may indicate false resistance. Proper storage and handling methods are suggested.
Antimicrobial Resistance and R Factors in
Salmonella
Isolated in California (1971–1972)
Authors: Bissett Marjorie L. , Abbott Sharon L. , Wood Ronald M.
Published: June 2012

The antimicrobial resistance of 2,246 strains of
Salmonella
isolated from humans in California was determined. Resistance to one or more of the 12 antimicrobial agents tested was found in 32% of the isolates.
Salmonella typhimurium
strains represented 31% of the serotypes isolated; 49% of these strains were resistant. Fifty-one percent of
S. heidelberg
, 42.5% of
S. newport
, and 40% of
S. saint paul
strains were resistant. Seventy-seven percent of all resistant serotypes were resistant to two or more of the antimicrobial agents tested. R factors were demonstrated in 70% of the multiply resistant strains. Resistance of the
Salmonella
strains to one or more of the 12 antimicrobials tested and the frequency of resistance to tetracycline and ampicillin were significantly greater than resistance reported in other studies performed in this country. Chloramphenicol resistance was encountered in 33 (1.5%) of the
Salmonella
isolates; 19 of these were
S. typhi
demonstrating a pattern of resistance to streptomycin, sulfisoxazole, tetracycline, and chloramphenicol and carrying an R factor capable of transferring the complete pattern of resistance.
Antibiotic Susceptibility of
Streptococcus bovis
and Other Group D Streptococci Causing Endocarditis
Authors: Thornsberry Clyde , Baker C. N. , Facklam R. R.
Published: June 2012

Seventy-four strains of
Streptococcus bovis
and 35 strains of enterococci (
Streptococcus faecalis
and its varieties,
Streptococcus faecium
and
Streptococcus durans
), most of which were isolated from patients with endocarditis, were tested for their susceptibility to penicillin, ampicillin, erythromycin, cephalothin, vancomycin, methicillin, tetracycline, chloramphenicol, kanamycin, streptomycin, and gentamicin. Minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) were determined by a microtiter broth dilution technique. All of these organisms are group D streptococci, but the
S. bovis
strains are not enterococci. On the basis of both MIC and MBC, the
S. bovis
strains were much more susceptibile in general to antibiotics then were the enterococcal strains. For the
S. bovis
strains, the lowest MICs were obtained with penicillin, ampicillin, and erythromycin, and the lowest MBCs with penicillin and ampicillin. Although these antibiotics were also the most active against the enterococci, the MICs and MBCs were much higher than obtained with the
S. bovis
strains. Gentamicin was the most active aminoglycoside. On the basis of in vitro susceptibility results, the
S. bovis
strains resemble the viridans streptococci rather than enterococci.
Susceptibility of Pathogenic Actinomycetes to Antimicrobial Compounds
Authors: Lerner Phillip I.
Published: June 2012

Current interest in antimicrobial susceptibility testing of anaerobic pathogens and recent recognition that actinomycetes other than
Actinomyces israelii
may cause actinomycosis in man prompted this in vitro survey of 74 strains of actinomycetes, representing seven species. Minimum inhibitory concentrations (MICs) for 24 antimicrobials were determined by inhibition of gross colonial enlargement in semisolid antibiotic agar after incubation at 37 C for 48 h under anaerobic conditions. Erythromycin and rifampin were the most active drugs in vitro (MICs of 0.008 to 0.25 μg/ml), although a small number of non-israelii strains were conspicuously more resistant to the latter (MICs >0.5 μg/ml). Penicillin G, cephaloridine, minocycline, and clindamycin were also very active in vitro (MICs of 0.03 to 1.0 μg/ml); for a few non-israelii strains the MICs of clindamycin were 2.0 to 8.0 μg/ml. MICs of cephalothin, ampicillin, lincomycin, tetracycline, doxycycline, and chloramphenicol were well within a therapeutic range for all strains of
A. israelii
and most other species, although the MIC of lincomycin against a few non-israelii strains and of tetracycline and doxycycline against the majority of these strains was 2.0 to 8.0 μg/ml. Oxacillin, dicloxacillin, and cephalexin were less active in vitro, particularly against strains other than
A. israelii
. Most non-israelii species were not suppressed by 125 μg of metronidazole per ml, which concentration inhibited all strains of
A. israelii;
otherwise, there were no antimicrobial susceptibility differences among the species tested. Aminoglycoside activity was negligible.
Herpes Simplex Virus Skin Infection in Hairless Mice: Treatment with Antiviral Compounds
Authors: Klein Richard J. , Friedman-Kien Alvin E. , Brady Eileen
Published: June 2012

A hairless mouse-herpes simplex virus skin infection experimental model was used to evaluate the efficacy of the antiviral compounds 9-β-
d
-arabinofuranosyladenine (ara-A), 5-iodo-2′-deoxyuridine (IUdR), and 6-azauridine (aza-U). Ara-A and IUdR, when administered intraperitoneally by several different dosage schedules, reduced the severity of cutaneous herpetic lesions and the incidence of paralysis and increased significantly the number of survivors. A more rapid healing of the lesions and an increase in the mean survival time also was observed. A delay of 24 to 48 h in the initiation of treatment after the infection was more effective than treatments started at the time of inoculation. Treatment with ara-A was somewhat superior to that with IUdR, but aza-U was totally ineffective. Enhancement of the evolution of the infection was noted after treatment with aza-U.
Inactivation of Herpes Simplex Virus by Thiosemicarbazones and Certain Cations
Authors: Levinson Warren , Coleman Virginia , Woodson Bruce , Rabson Alan , Lanier Jeff , Whitcher Jack , Dawson Chandler
Published: June 2012

We demonstrated that herpes simplex virus types 1 and 2, including a type 2 strain which transforms hamster cells in vitro, and
Herpesvirus saimiri
are inactivated by exposure to thiosemicarbazones. Because thiosemicarbazones are thought to interact with heavy metals in this inactivation process (9), we tested and found some of these herpesviruses to be susceptible to exposure to certain heavy metals. A virion polymerase was sought because the ribonucleic acid (RNA)-dependent deoxyribonucleic acid (DNA) polymerase of Rous sarcoma virus and the DNA-dependent RNA polymerase of vaccinia virus are inhibited. However, neither DNA nor RNA polymerase activity could be demonstrated in herpes simplex virions. The ability of thiosemicarbazone to ameliorate the course of herpes simplex virus infection in rabbit eyes was observed, but was considered insufficient to be of clinical importance.
Regulation of the Formation of Alkaline Phosphatase During Neomycin Biosynthesis
Authors: Bandyopadhyay Susanta Kr. , Majumdar S. K.
Published: June 2012

The use of a washed-cell system to study the factors controlling the synthesis of alkaline phosphatase and neomycin by
Streptomyces fradiae
has shown that calcium and magnesium salts are stimulatory, with maximal synthesis of both achieved with a combination of these salts. Among all the carbon sources studied, only arabinose induces alkaline phosphatase synthesis, whereas glucose and other carbon sources inhibit the synthesis of the enzyme. Asparagine is a very good inducer of enzyme and neomycin synthesis, with lysine and alanine having lower stimulatory effects. The appearance of alkaline phosphatase is due to de novo protein synthesis as demonstrated by the inhibition of its synthesis in the presence of chloramphenicol. There is a good correlation between the synthesis of alkaline phosphatase and neomycin biosynthesis.
Amikacin (BB-K8) Treatment of Multiple-Drug-Resistant
Proteus
Infections
Authors: Sharp Philip M. , Saenz Corando A. , Martin R. Russell
Published: June 2012

The new aminoglycoside antibiotic, amikacin (formerly called BB-K8), was used to treat 12 episodes of urinary tract infection caused by hospital-acquired
Proteus rettgeri
strains. These bacteria were resistant in vitro to kanamycin and gentamicin, and infection persisted in most of the patients in spite of therapy with one of these agents. In all cases, the urinary tract infection was controlled or eradicated by therapy, although relapse or reinfection was frequently encountered in these patients with complicated urological problems. No toxicities attributable to the drug were encountered in the small group of patients.
Microbiological Agar Diffusion Assay for Metronidazole Concentrations in Serum
Authors: Levison Matthew E.
Published: June 2012

An agar diffusion method using paper disks on plates seeded with
Clostridium perfringens
and incubated anaerobically to assay serum levels of metronidazole is described. The lowest serum metronidazole concentration that could be measured was 0.7 μg/ml, and the average error was 4% for 5 μg/ml. This assay could measure metronidazole in the presence of gentamicin or in the presence of penicillin, with the use of penicillinase incorporated into the assay plates, or in presence of penicillin, methicillin, and cephalothin with prior exposure of the specimen to beta-lactamase.
Antileishmanial Effect of Allopurinol
Authors: Pfaller Michael A. , Marr J. Joseph
Published: June 2012

Allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine) has been shown to inhibit the growth of
Leishmania braziliensis
in vitro at concentrations which are attainable in human tissues and body fluids. This compound is believed to act by interdicting the de novo synthesis of pyrimidines, probably through the formation of allopurinol ribotide. Its lack of toxicity makes it a potential candidate for animal experimentation and it may serve as a prototype for other agents with similar mechanisms of action.
Synergy Between Cephalosporin and Aminoglycoside Antibiotics Against
Providencia
and
Proteus
Authors: Hyams Phineas J. , Simberkoff Michael S. , Rahal James J.
Published: June 2012

Clinical isolates of
Providencia
and
Proteus
with relative aminoglycoside resistance were tested for susceptibility to combinations of gentamicin or tobramycin with cephalothin or cefazolin. The minimal bactericidal concentration of aminoglycoside for one-third of the strains was reduced by fourfold or more in the presence of one-fourth of the minimal bactericidal concentration of either cephalosporin. This effect was achieved by clinically attainable concentrations of cephalothin or cefazolin.
Technique for Determining the Bactericidal Effect of Drug Combinations
Authors: Lorian Victor , Fodor Georgeta
Published: June 2012

Two paper strips, each containing different antimicrobial agents, were placed on plates on Mueller-Hinton agar to permit antibiotic to enter the agar. A filter membrane was placed on this plate, and the microorganisms were planted on the membrane. After 6 h of incubation at 37 C, the membrane was transferred to antibiotic-free Mueller-Hinton agar containing triphenyltetrazolium hydrochloride and incubated for 18 h at 37 C. Specific growth patterns were indicative of additive (indifferent), synergistic, or antagonistic effects of the drug combination used. Trimethoprim and sulfamethoxazole proved to act synergistically against 85% of
Escherichia coli
, 86% of
Klebsiella
, and 89% of
Proteus mirabilis
strains tested. A few strains resistant to either drug were susceptible to their combination. The technique was useful against organisms with widely differing susceptibilities to the two antimicrobial agents tested.
Inhibition of [
14
C]Chloramphenicol Binding to
Escherichia coli
Ribosomes by Erythromycin Derivatives
Authors: Pestka Sidney , LeMahieu Ronald A.
Published: June 2012

The effect of erythromycin A and 35 analogues of erythromycin A on [
14
C]chloramphenicol binding to
Escherichia coli
ribosomes was evaluated. Substitutions on various portions of the erythromycin molecule were made with retention of ability to bind to ribosomes. Specifically, substantial activity in interference with [
14
C]chloramphenicol binding was retained upon removal of the cladinose and various substitutions on the 3-hydroxyl, the oxime, and 2-hydroxyl groups. Erythromycin analogues with relatively poor binding activity to ribosomes could be detected. This assay can be used alone or in conjunction with microbiological assays for screening of active analogues. It permits an estimate of the general binding activity of compounds rapidly and directly. The assay reflects the ability of the compounds to interact with their target organelle, the ribosome, and may serve as a useful adjunct in developing new compounds.
Mutanolysin, Bacteriolytic Agent for Cariogenic Streptococci: Partial Purification and Properties
Authors: Yokogawa Kanae , Kawata Shigeo , Nishimura Shinzo , Ikeda Yasuhiko , Yoshimura Yoshio
Published: June 2012

Mutanolysin partially purified from the culture filtrate of
Streptomyces globisporus
1829 consists of two main lytic enzymes with an isoelectric point near pH 8.5 and 10, respectively, and proteolytic enzyme is associated with the latter lytic enzyme. Mutanolysin exhibited maximal lytic activity at 60 C in the pH range 6.5 to 7.0 and was stable at 50 C in the acid range.
N
-bromosuccinimide caused complete inhibition of lytic activity at 1 mM, whereas calcium and magnesium ions at the same concentration caused activation. Mutanolysin had lytic or bactericidal activity against the living cells of
Streptococcus mutans, Streptococcus salivarius, Streptococcus sanguis, Lactobacillus acidophilus
, and
Actinomyces viscosus
, which are considered to be etiologic agents of dental caries, but had no activity against
S. aureus
and all gram-negative strains tested. The lytic activity was well retained in human saliva. Digestion of the cell walls of
S. mutans
BHT by mutanolysin was accompanied by the liberation of free amino groups and reducing sugars. Mutanolysin may be expected to be a useful agent for dental caries control.
Properties of R Plasmids Determining Gentamicin Resistance by Acetylation in
Pseudomonas aeruginosa
Authors: Jacoby George A.
Published: June 2012

Two clinical isolates of
Pseudomonas aeruginosa
, one a pyocin type 5 strain from Atlanta, could transfer gentamicin resistance by conjugation. Donor and recipient strains inactivated gentamicin by acetylation. The R plasmids, pMG1 and pMG2, also determined resistance to sisomicin, another substrate of gentamicin acetyltransferase I, sulfonamides, and streptomycin, but not resistance to kanamycin, neomycin, tobramycin, butirosin, or BB-K 8. They were transmissible to many strains of
P. aeruginosa
, including a Rec
−
strain, but not to
Escherichia coli
or other enterobacteriaceae. These R plasmids were compatible with R plasmids transmissible to
P. aeruginosa
from
E. coli
, including members of C, N, P, and W incompatibility groups. From a strain carrying pMG1 and a compatible plasmid, pMG1 was transferred independently but transfer of the second plasmid often resulted in cotransfer of pMG1. In contrast, pMG1 and pMG2 were incompatible with pseudomonas R plasmids R931 and R3108, and with R931 they readily formed recombinant plasmids. The four plasmids in this incompatibility group determine additional biological properties, including resistance to inorganic and organic mercury compounds, to ultraviolet light, and to certain deoxyribonucleic acid phages. pMG1 and pMG2 also phenotypically inhibited pyocin production. Consequently such R plasmids alter the phage and pyocin types of their host strains.
In Vivo Effect of Thiolutin on Cell Growth and Macromolecular Synthesis in
Escherichia coli
Authors: Khachatourians G. G. , Tipper D. J.
Published: June 2012

Thiolutin reversibly inhibits growth and ribonucleic acid synthesis in
Saccharomyces cerevisiae
. It is now demonstrated that, at 5 μg/ml, thiolutin rapidly inhibits all incorporation of radioactive precursors into ribonucleic acid and protein in
Escherichia coli
, although the incorporation of deoxythymidine into deoxyribonucleic acid continues for some time. Concentrations of thiolutin of 5 μg/ml and above are bacteriostatic and do not lead to unbalanced growth, so that cell size remains constant. The antibiotic and its inhibitory effects are easily removed by washing, whereupon macromolecular synthesis and cell division resume unimpeded. These data are consistent with reversible inhibition of ribonucleic acid synthesis being the primary mode of action of thiolutin in
E. coli
, and suggest that thiolutin may be a useful tool for studies where such reversible inhibition is required.
Inactivation of Endotoxin by Polymyxin B
Authors: Cooperstock Michael S.
Published: June 2012

The limulus gelation assay was utilized to investigate endotoxin inactivation by a number of antibiotics in vitro. Endotoxin activity was sharply reduced by polymyxin B and sodium colistimethate. The effect of the polymyxin was not significantly inhibited by 0.001 M calcium or 90% serum. Crude endotoxins from a variety of aerobic gram-negative bacteria, including several not previously studied, could be inactivated 1 or more logs by as little as 1 μg of polymyxin B per ml, whereas
Bacteroides fragilis
endotoxin was poorly detoxified. A 10,000-fold range in the relative susceptibility of different endotoxins to inactivation by polymyxin B was found. The endotoxin most susceptible to polymyxin B was derived from an organism resistant to polymyxin B by disk sensitivity testing, suggesting that the bacteriocidal and endotoxin detoxifying properties of polymyxin need not be directly related.
Biliary Tract Excretion of Cefazolin, Cephalothin, and Cephaloridine in the Presence of Biliary Tract Disease
Authors: Ratzan Kenneth R. , Ruiz Carlos , Irvin George L.
Published: June 2012

The biliary tract excretion of three cephalosporins, cefazolin, cephaloridine, and cephalothin, was compared in patients with biliary tract disease. In the absence of obstruction, mean antibiotic levels in bile from gall bladder and common duct in patients undergoing cholecystectomy were highest for cefazolin (17 and 31 μg/ml, respectively) than either cephaloridine (7 and 9 μg/ml) or cephalothin (1 and 4 μg/ml). Biliary tract levels generally paralleled serum levels. In no patient with cystic duct obstruction were any of the cephalosporins detectable in appreciable amounts in gall bladder bile. In patients with T-tube drainage given each of the three different cephalosporins on separate days, concentrations of cefazolin in bile were many-fold higher than either cephaloridine or cephalothin. Peak levels of cefazolin in T-tube bile averaged 51 μg/ml after intravenous and 26 μg/ml after intramuscular administration, whereas mean peak levels of cephalothin and cephaloridine were only 6 and 16 μg/ml, respectively. Here, too, T-tube levels reflected serum concentrations and obstruction to biliary flow impaired excretion of each of the drugs.
Comparative Activity of Tobramycin, Amikacin, and Gentamicin Alone and with Carbenicillin Against
Pseudomonas aeruginosa
Authors: Kluge Ronica M. , Standiford Harold C. , Tatem Beverly , Young Viola M. , Greene William H. , Schimpff Stephen C. , Calia Frank M. , Hornick Richard B.
Published: June 2012

The effect of gentamicin against 130 clinical isolates of
Pseudomonas aeruginosa
was compared with that of two investigational aminoglycoside antibiotics, tobramycin and amikacin. Minimal inhibitory concentration data indicated that, on a weight basis, tobramycin was two to four times as active as gentamicin against most isolates. However, 14 of 18 organisms highly resistant to gentamicin (≥80 μg/ml) were also highly resistant to tobramycin. Amikacin was the least active aminoglycoside on a weight basis, but none of the isolates were highly resistant to this antibiotic. When therapeutically achievable concentrations were used, adding carbenicillin to gentamicin or to tobramycin enhanced inhibitory activity against those isolates susceptible (≤5 μg/ml) or moderately resistant (10 to 40 μg/ml) to the aminoglycoside. Such synergy was seldom demonstrated for isolates highly resistant to gentamicin or tobramycin. The combination of carbenicillin and amikacin enhanced inhibition against all but two of the isolates. Both tobramycin and amikacin offer in vitro advantages over gentamicin against
P. aeruginosa
.
Empirical Equation for Pharmacokinetic Analysis of Drug Serum Levels After Oral Application
Authors: Engberg-Pedersen H.
Published: June 2012

The equation log(concentration) =
a
+
b
/ [Formula: see text] +
c
· [Formula: see text] +
d
·(
T
− φ) was used to calculate serum level curves from individual data sets of drug serum concentrations, obtained from experiments with orally administered drugs. These curves were subsequently used to calculate peak values, times for onset of peak, area, and other pharmacokinetic parameters that ought to be independent of any preconceived theory about the behavior of the drug in the system. A program is described by which parameters for individual data sets can be calculated and a mean curve with a peak value, time for onset of peak, and area equal to the arithmetic mean of the corresponding values for the participating subjects, is produced. The results of this method are compared to those of the “one-compartment model with lag time” and shown to be superior in all the test cases. In particular, the proposed method performs well with data from a highly protein-bound drug, for which the one-compartment model fails completely. Data sets of six to eight samples taken over the entire period of detectable serum levels, with 10% analytical error in the results, gave estimates of peak value and area with a coefficient of variation of 6 to 9%, whereas the variation in the estimates for different subjects in a treatment group amounted to 20 to 60%. This shows that the proposed method, although able to cope with a short series of imprecise measurements available in practical work, is still sufficiently sensitive to detect real differences between the individual subjects.
Pharmacology of Cephalothin in the Biliary Tract of Humans
Authors: Mendelson J. , Portnoy J. , Sigman H. , Dick V.
Published: June 2012

Serum and biliary tract levels of cephalothin were determined in a large series of patients. Serum cephalothin levels in the therapeutic range were present at 1 h after a single dose of the antibiotic in only 4 of 39 (10.3%) subjects. Therapeutic bile cephalothin levels were achieved in only 2.4% of all subjects, and this occurred between 40 and 70 min after the administration of the antibiotic.
Enhancement of the Effects of Anti-Staphylococcal Antibiotics by Aminoglycosides
Authors: Watanakunakorn Chatrchai , Glotzbecker Cheryl
Published: June 2012

The in vitro activity of seven anti-staphylococcal antibiotics alone and in combination with four aminoglycoside antibiotics against 35 clinical isolates of
Staphylococcus aureus
from blood cultures of patients with endocarditis or septicemia was studied. The combination of nafcillin-gentamicin or nafcillin-tobramycin when compared with nafcillin alone killed significantly more
S. aureus
at 6 h for 33 of 35 isolates. A significant decrease in viable colony-forming units at 24 and 48 h was demonstrated for a smaller number of isolates. Using the agar dilution antibiotic susceptibility test, significant enhancement of activity was demonstrated against almost all isolates when cephalothin, cefazolin, or clindamycin was combined with gentamicin, tobramycin, or kanamycin. The combination of nafcillin or vancomycin with gentamicin, tobramycin, or kanamycin also showed enhanced activity against the majority of isolates. Oxacillin or methicillin when combined with the aminoglycosides showed enhancement of activity against the least number of isolates. Streptomycin was the least effective of the four aminoglycoside antibiotics studied.
Phosphorylation of Kanamycin, Lividomycin A, and Butirosin B by
Providencia stuartii
Authors: Marengo Paul B. , Chenoweth Maymie E. , Overturf Gary D. , Wilkins Jeanette
Published: June 2012

The isolation of
Providencia stuartii
resistant to multiple aminoglycoside antibiotics prompted an investigation into the mechanism of their resistance. Crude enzyme extracts of a strain of
P. stuartii
inactivated kanamycin, lividomycin A, and butirosin B in the presence of adenosine 5′-triphosphate (ATP), as measured by a microbiological assay. The occurrence of inhibitory concentrations of 500 μg or greater per ml against kanamycin, lividomycin A, and butirosin B, coupled with the inactivation of these antibiotics in the presence of ATP, suggested enzymatic phosphorylation. This was documented by the transfer of the γ-phosphate of [γ-
32
P]ATP. In contrast, the inability to inactivate gentamicin or tobramycin by the crude enzyme extracts in the presence of ATP suggests another enzymatic mechanism of resistance for these antibiotics, such as adenylation or acetylation. Of importance is the fact that amikacin, a semisynthetic analogue of kanamycin A which is resistant to inactivation by most resistance transfer factor enzymes, was found to inhibit the growth of
P. stuartii
at low concentrations.
Identification of Harper-Cawston Factor as Thymidine Phosphorylase and Removal from Media of Substances Interfering with Susceptibility Testing to Sulfonamides and Diaminopyrimidines
Authors: Ferone R. , Bushby S. R. M. , Burchall J. J. , Moore W. D. , Smith D.
Published: June 2012

Rich media support the growth of bacteria in the presence of concentrations of sulfonamides and diaminopyrimidines that are highly inhibitory when the organisms are grown on minimal media. Many such rich media can be made more suitable for susceptibility testing by the incorporation of lysed horse blood. Harper and Cawston characterized the active substance, Harper-Cawston factor (HCF), and later studies indicated it to be a protein. It has now been identified as thymidine phosphorylase. The identification follows from the identical purification pattern of HCF and thymidine phosphorylase activities from horse blood to a high degree of purity. Blood of goats, sheep, oxen, geese, chickens, cows, dogs, rats, and humans had neither biological activity. The identification of HCF as thymidine phosphorylase is consistent with the earlier findings of Koch and Burchall (1971) that most of the interfering effects of rich media could be accounted for by their thymidine contents, and that thymidine is much more active in this respect than is thymine.
Susceptibility of Anaerobes to Cefoxitin and Other Cephalosporins
Authors: Tally Francis P. , Jacobus Nilda V. , Bartlett John G. , Gorbach Sherwood L.
Published: June 2012

The in vitro susceptibility of 155 strains of anaerobic bacteria to five cephalosporin antibiotics was tested. Cefoxitin was the most active against 33 isolates of
Bacteroides fragilis
; 82% of the strains were sensitive at 16 μg/ml. At 64 μg/ml cefazolin and cephaloridine were also generally effective. Cephalothin and cephalexin were relatively inactive versus
B. fragilis
. Cefoxitin, cephaloridine, cefazolin, and cephalothin showed comparable activity against 122 strains of anaerobes other than
B. fragilis
. More than 90% of the strains were sensitive to each of these antimicrobials at 16 μg/ml. Cephalexin was the least effective cephalosporin against all species tested.
Cinoxacin: In Vitro Antibacterial Studies of a New Synthetic Organic Acid
Authors: Lumish Robert M. , Norden Carl W.
Published: June 2012

Cinoxacin (compound 64716) is a synthetic organic acid with antibacterial activity against most aerobic gram-negative bacilli. Minimal inhibitory concentrations of cinoxacin (agar-dilution method) were determined for 419 strains.
Escherichia coli
was the most susceptible group of organisms. The majority of
Klebsiella
sp.,
Enterobacter
sp.,
Proteus
sp., and
Serratia marcescens
were inhibited by 8 μg of cinoxacin per ml.
Pseudomonas aeruginosa
and all gram-positive isolates tested were resistant to 64 μg or less of cinoxacin per ml. Zones of inhibition using a 30-μg disk correlated well with agar-dilution minimal inhibitory concentrations (r = −0.9). Cinoxacin was bactericidal when tested with inocula of 5 × 10
6
organisms per ml. Resistance to cinoxacin was readily developed in all three strains tested by serial passage on drug-containing agar. The in vitro properties of this agent were similar to those of nalidixic acid.
Comparative Effects of Amoxycillin and Ampicillin in the Treatment of Experimental Mouse Infections
Authors: Comber K. R. , Osborne Christine D. , Sutherland R.
Published: June 2012

Amoxycillin was significantly more active than ampicillin in the treatment of intraperitoneal mouse infections when administered by oral and parenteral routes, although the causal bacteria were equally susceptible in vitro to the two penicillins. Amoxycillin produced higher antibiotic blood concentrations in mice than ampicillin after oral administration, and this was a possible explanation for the superior oral activity of amoxycillin. In contrast, antibiotic blood concentrations were the same for both compounds after subcutaneous injection, but it was demonstrated that amoxycillin was more effective than ampicillin by this route in reducing bacterial counts in the peritoneal cavity and in the blood of mice infected with
Escherichia coli
. Amoxycillin was also significantly more active than ampicillin in the treatment of infection by intraperitoneal dosing as a result of greater bactericidal activity in infected mice together with the production of higher antibiotic blood levels. The results of these studies on the effects of parental treatment of experimental infections with the two penicillins show that the superior chemotherapeutic activity of amoxycillin was associated with the greater bactericidal activity of amoxycillin in vivo and with differences in the distribution of the two penicillins in the infected animal.