bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of
Escherichia coli
Mutants to Evaluate Purines, Purine Nucleosides, and Analogues
Authors: Hill Donald L. , Pittillo Robert F.
Published: June 2012

Of 142 purines, purine nucleosides, and analogues tested for inhibition of growth of
Escherichia coli
B Hill, 45 were active. Of these, 27 were evaluated for inhibition of other
E. coli
lines, including those resistant to 6-thioguanine, 2-fluoroadenosine, 2,6-diaminopurine, or 6-mercaptopurine. Most toxic to the parent lines were 2-fluoroadenosine, 2-fluoroadenine, 2-fluoro-5′-deoxyadenosine, adenosine, 6-thioguanosine, 6-thioguanine, 6-mercaptopurine, 6-mercaptopurine ribonucleoside, 2-azaadenine, 2′-deoxyinosine, 6-
N
-aminoadenine, and inosine. Hypoxanthine was strongly inhibitory only to
E. coli
B Hill. Evidence regarding the substrate specificity of the three purine phosphoribosyltransferases was obtained by assaying for these enzymes in extracts of the various cell lines and by cross-resistance studies. The line selected for resistance to 6-thioguanine had low guanine phosphoribosyltransferase activity (guanosine monophosphate: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) and was deficient in activity for xanthine and 6-thioguanine. The lines selected for resistance to 2-fluoroadenosine and 2,6-diaminopurine were deficient in adenine phosphoribosyltransferase activity (adenosine monophosphate: pyrophosphate phosphoribosyltransferase, EC 2.4.2.7), and that selected for resistance to 6-mercaptopurine had low hypoxanthine phosphoribosyltransferase activity and undetectable activity with 6-mercaptopurine as a substrate. Purine, 6-methylpurine, 2-fluoroadenine, 2,6-diaminopurine, and 2-azaadenine were classified as adenine analogues; 6-mercaptopurine and 8-aza-2,6-diaminopurine, as hypoxanthine analogues; and 6-thioguanine and 2-amino-6-chloropurine, as analogues of guanine. The inhibition of bacterial growth by hypoxanthine, inosine, 2′-deoxyinosine, or adenosine was prevented by small amounts of thiamine or by relatively high concentrations of either cytidine or uridine. Cytidine also reversed the inhibition by some purine and purine ribonucleoside analogues. Orotate phosphoribosyltransferase (OMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.10), a possible site of action for these compounds, was not inhibited directly by the toxic agents.
Comparative Activity of Amoxycillin and Ampicillin in an Experimental Bacterial Infection in Mice
Authors: Hunter Pamela A. , Rolinson G. N. , Witting Doreen A.
Published: June 2012

Against experimental infections in mice with strains of
Escherichia coli
and with
Proteus mirabilis
, amoxycillin was found to be more active than ampicillin both by the oral and the subcutaneous routes of administration. With the bacteria used in these experiments, ampicillin and amoxycillin showed the same minimal inhibitory concentrations and, after subcutaneous administration, the levels of ampicillin and amoxycillin in the plasma and tissue homogenate were also similar. However, counts of the number of viable bacteria present in the infected tissue showed that amoxycillin exerted a more rapid and a more marked bactericidal effect than did ampicillin, and this could be correlated with the difference in therapeutic effect. When given by mouth, amoxycillin was more completely absorbed than ampicillin and gave rise to higher levels of antibiotic in the plasma. This may have accounted in part for the difference in therapeutic activity seen when these penicillins were given by the oral route. However, when appropriate oral dosages of ampicillin and amoxycillin were used so as to achieve similar levels of antibiotic in the plasma and tissue homogenate, amoxycillin was again found to exert a more marked bactericidal effect than did ampicillin, and this was accompanied by greater therapeutic activity. In experiments in vitro, amoxycillin also showed a more rapid bactericidal effect than did ampicillin against the bacteria which were used to produce the experimental infections.
Amphotericin B Therapy in an Anephric Patient
Authors: Feldman Harvey A. , Hamilton John D. , Gutman Robert A.
Published: June 2012

Serum levels of amphotericin B were serially determined during and after a course of therapy in an anephric patient who developed systemic candidiasis after an unsuccessful renal transplantation. There was no progressive accumulation of drug in serum, and the pattern of disappearance of drug from serum was similar to that published for patients with normal renal function. The dialyzability of amphotericin B was studied in vivo during a 6-h period of hemodialysis, by an in vitro dialysis of amphotericin B in water by using similar equipment, and a Pellicon membrane filter which retains molecular species of 100,000 molecular weight and higher. These studies revealed that the drug is not dialyzable with conventional hemodialysis membranes, regardless of protein binding in plasma, and is excluded from passing through the Pellicon membrane filter.
Selective Filtration of Antibiotics Through Collodion Membranes
Authors: Barza Michael , Bergeron Michel G. , Brusch John , Weinstein Louis
Published: June 2012

Marked differences were noted among 14 antibiotics in their filterability through collodion (nitrated cellulose) membranes. The findings could not be attributed to differences in molecular weight or degree of serum protein binding, although the latter factor imposed an additional restraint on the passage of certain agents. Poorly filtered antibiotics appeared to be absorbed by the collodion. Some of these observations might be accounted for by the known ability of nitrated cellulose to interact with anions. However, the extreme differences in filterability among the various penicillins and the very restricted passage of certain cationic antibiotics appeared to be better explained by intrinsic differences in the diffusibility of these agents through water. Although differential filtration offers a means of assaying samples containing certain mixtures of antibiotics, the degree of separation exhibited by collodion membranes is not sufficient to make them useful for clinical purposes.
Structure-Activity Relationships Among the Aminoglycoside Antibiotics: Role of Hydroxyl and Amino Groups
Authors: Benveniste R. , Davies J.
Published: June 2012

The close structural similarity of several of the deoxystreptamine-containing aminoglycoside antibiotics (gentamicins, neomycins, kanamycins, tobramycin) and the recent isolation of enzymatically
N
-acetylated aminoglycosides have permitted a systematic comparison of the structure-activity relationships in this group of antibiotics. The number and location of amino groups on the hexoses and the site of attachment of the other rings to deoxystreptamine have been shown to exert a profound effect on the ability of these compounds to inhibit or to cause misreading of polypeptide synthesis in vitro. The conclusions allow certain predictions to be made concerning the interaction of these compounds with the bacterial ribosome.
In Vitro Antiviral Activity and Preliminary Clinical Trials of a New Adamantane Compound
Authors: Mathur Asha , Beare A. S. , Reed Sylvia E.
Published: June 2012

A compound, 1′-methyl spiro (adamantane-2,3′-pyrrolidine) maleate, chemically related to the antiviral drug amantadine, was tested for activity in vitro against a number of human respiratory viruses. By a variety of techniques, it was shown to be active against a wide range of human and animal influenza A viruses. The effect was, however, variable and ranged from high activity against two 1957 Asian strains to no observable activity against a 1971 strain. Like amantadine, the drug did not inhibit the growth of influenza B viruses. It was also inactive against a number of paramyxoviruses. Unlike amantadine, the drug did inhibit rhinoviruses, but to a lesser extent than myxoviruses. The coronavirus 229E was also sensitive to the action of the drug in vitro. Although an earlier trial in volunteers showed that, when given orally from 2 days before until 5 days after virus challenge, the drug was protective against infection with influenza A/Hong Kong/68 virus, a similar trial in volunteers challenged with rhinoviruses 2 and 9 revealed no useful activity against rhinoviruses in man.
Tobramycin Concentrations During Peritoneal Dialysis
Authors: Weinstein Allan J. , Karchmer Adolf W. , Moellering Robert C.
Published: June 2012

A patient undergoing peritoneal dialysis for severe renal failure was treated with tobramycin. Peritoneal dialysis was inefficient in removing tobramycin from the serum. Tobramycin concentrations in the dialysis effluent were low. Despite acute oliguric renal failure, urine concentrations of tobramycin were sufficient to treat most gram-negative urinary tract infections.
Interrelationships Between Disk and Tube Dilution Sensitivity Tests for the Aminoglycoside Antibiotics Gentamicin, Kanamycin, Sisomicin, and Tobramycin
Authors: Waitz J. Allan
Published: June 2012

Poor statistical correlation was obtained between tube dilution test results and disk test results by using standard procedures. Significant regressions were obtained although they were not linear. Different regressions were obtained with different bacterial species. It is suggested that for the aminoglycosides studied (gentamicin, kanamycin, tobramycin, and sisomicin) both disk and dilution tests are useful in separating resistant from sensitive organisms. However, poor relationships were obtained between the two test types among sensitive organisms.
Isolation and Characterization of a Bacteriocin from a Homofermentative
Lactobacillus
Authors: Upreti G. C. , Hinsdill R. D.
Published: June 2012

Nearly 100 isolates of
Lactobacillus
were obtained from human and animal sources. Screening tests with the isolates revealed seven possible bacteriocinogenic strains and 26 strains sensitive to one or more of these inhibitory strains. Three homofermentative strains were selected for additional study after it was shown that their inhibitory substances differed in activity spectrum and in susceptibility to inactivation by proteolytic enzymes. One of these,
L. helveticus
strain LP27, was shown to produce a potent bacteriocin called lactocin 27. The lactocin was isolated from the culture supernatant fluid as a protein-lipopolysaccharide complex. In the presence of sodium dodecyl sulfate the complex was dissociated, and the activity was found to reside in a small glycoprotein (molecular weight 12,400). The amino acid composition of purified lactocin 27 is similar to that of the
L. fermenti
bacteriocin; neither requires disulfide bonds for activity.
Streptococcal Pharyngitis Therapy: Comparison of Clindamycin Palmitate and Potassium Phenoxymethyl Penicillin
Authors: Stillerman Maxwell , Isenberg Henry D. , Facklam Richard R.
Published: June 2012

Clindamycin palmitate and potassium phenoxymethyl penicillin were evaluated in 103 children with upper respiratory illnesses and pharyngeal group A streptococci, from November 1970 to July 1971. The children were assigned randomly by weight to one of the antibiotic regimens given orally for 10 days. Clindamycin palmitate and potassium phenoxymethyl penicillin dosages were 75 and 125 mg, respectively, in 5 ml tid for children weighing less than 25 kg, and 150 and 250 mg, respectively, in 10 ml bid for children weighing 25 kg or more. Recurrences of the original streptococcal group A, M, and T types within 3 weeks after the end of treatment were classified as failures. The failure rates were: clindamycin palmitate, 10% (5 of 52), and potassium phenoxymethyl penicillin, 18% (9 of 51). Possible drug-related rashes were observed in 8 of 52 clindamycin palmitate-treated patients. The geometric mean minimal inhibitory concentrations of clindamycin and penicillin against 103 isolates of group A streptococci were 0.033 and 0.007 μg/ml, respectively. The serum concentrations about 70 min after ingesting 150 mg of clindamycin palmitate averaged 3.8 μg/ml and after 250 mg of potassium phenoxymethyl penicillin averaged 0.9 μg/ml. Clindamycin palmitate was as effective as potassium phenoxymethyl penicillin in eradicating group A streptococci from the pharynx in tid and bid regimens. Nevertheless, because of its rash-producing tendency in some patients and higher cost, clindamycin palmitate should not be preferred to penicillin for treatment of streptococcal sore throat in the non-penicillin-allergic patient.
Clinical Studies of Cefazolin and Comparison with Other Cephalosporins
Authors: Madhavan T. , Quinn Edward L. , Freimer Earl , Fisher Evelyn J. , Cox Frank , Burch Keith , Pohlod Donald
Published: June 2012

Cefazolin, a new cephalosporin derivative, was studied in the treatment of 105 hospitalized patients with a variety of infections including endocarditis, pneumonia, and urinary and soft tissue infections, and was found to be effective in 104 patients. Cefazolin was also tested in vitro and shown to be effective against staphylococci, pneumococci,
Escherichia coli, Klebsiella
sp., and
Proteus mirabilis
by agar dilution method. It was shown to produce high serum levels when administered in a 250- to 1,000-mg intramuscular dose and was well tolerated and free from renal toxicity. Comparison of the results of this study with those from our prior studies on cephaloridine revealed equivalent antibiotic potency, good tolerance to both the agents when given intramuscularly, superior, average blood levels with cefazolin, equal clinical efficacy, and absence of renal toxicity with cefazolin (unlike cephaloridine). Similarly, the results of treatment of pneumococcal pneumonia with intramuscular cefazolin were found to be superior to those for oral cephalexin.
Nalidixic Acid Susceptibility Testing of Clinical Isolates of
Serratia marcescens
Authors: Jollick J. D. , Schervish-Swierkosz Ella M. , Brown W. J.
Published: June 2012

Nalidixic acid (nal) susceptibility of clinical isolates of
Serratia marcescens
from urinary tract infections, wounds, and blood was determined by the standard disk method, and results were compared with results obtained by a standardized tube dilution procedure using five different broth media. An attempt was made to approximate in vivo conditions by using urine as a test medium and correlating the activity of nal in urine with its activity in nutrient, Trypticase soy, brain-heart infusion, and Mueller-Hinton broths. The isolates were consistently susceptible to lower concentrations of nal in nutrient broth than in the other media. The results showed that Mueller-Hinton broth most closely reflected nal activity in urine. A standardized procedure for nal susceptibility testing of urinary tract isolates of
S. marcescens
is proposed.
In Vitro Sensitivity of
Salmonella
to Ten Antimicrobial Agents Including Sulfamethoxazole and Trimethoprim, Alone and in Combination
Authors: Marks Melvin I. , Kazemi M. , MacKay Elaine
Published: June 2012

The activities of trimethoprim (TMP) and sulfamethoxazole (SMZ), alone and in combination (SMZ-TMP), and of the following antibiotics were tested against 115 clinical isolates of nontyphoid
Salmonella
species: tobramycin, gentamicin, ampicillin, amoxicillin, neomycin, kanamycin, chloramphenicol, and tetracycline. The methods of disk diffusion, microtiter broth dilution, and agar dilution were employed for all single antimicrobial agents as well as for SMZ-TMP studies. Growth curves were performed in broth. SMZ-TMP, TMP, gentamicin, tobramycin, and neomycin were the most active drugs in vitro. All strains were inhibited by ≤1 μg of TMP per ml, but >100 μg of SMZ per ml was required for at least 10% of strains. SMZ and TMP in a ratio of 10:0.5, respectively, inhibited all isolates and were synergistic for 105 strains. All strains inhibited by the combination of 10:0.5 SMZ-TMP had a zone diameter of ≥22 mm by using a combination disk containing 1.25 μg of TMP and 23.75 μg of SMZ. Seven isolates were resistant to >100 μg/ml of ampicillin or amoxicillin; all isolates were sensitive to chloramphenicol at ≤6.3 μg/ml. SMZ-TMP appears to be active against nontyphoid salmonellae in vitro; this is usually due to a synergistic effect.
Effect of Rifampin on Cutaneous Hypersensitivity to Purified Protein Derivative in Humans
Authors: Mukerjee P. , Schuldt S. , Kasik J. E.
Published: June 2012

The effect of rifampin on cutaneous hypersensitivity was studied in 11 tuberculous patients. A suppressive effect was noted in eight patients, five of whom developed a negative response to the strength of purified protein derivative to which they had been shown to be previously sensitive. In one instance complete anergy to purified protein derivative was noted. It appears that rifampin has immunosuppressive effects in some patients when used in conventional doses.
In Vitro Effect of Virazole Against Influenza Viruses
Authors: Togo Yasushi
Published: June 2012

The minimal inhibitory concentrations of Virazole against 32 mean tissue culture infective doses of three type A influenza strains including type A/England/42/72 (H3N2) and a type B strain in tissue culture were 0.1 and 0.05 μg/ml, respectively. The growth inhibition pattern by various Virazole concentrations of type A virus was similar to that of the type B virus. Virazole appears to be slightly more potent against the A/England/42/72 strain than are other antiinfluenzal agents.
Sulfhydryl Reactivity: Mechanism of Action of Several Antiviral Compounds—Selenocystine, 4-(2-Propinyloxy)-β-Nitrostyrene, and Acetylaranotin
Authors: Billard William , Peets Edwin
Published: June 2012

The addition of 5 mM dithiothreitol to a cell-free assay system for influenza ribonucleic acid (RNA) polymerase activity reverses the inhibitory activity otherwise possessed by three established antiviral compounds: selenocystine, 4-(2-propinyloxy)-β-nitrostyrene, and acetylaranotin. Although 50% or greater enzyme inhibitory activity is repeatedly achieved for these compounds at a concentration of approximately 50 μg/ml (0.1 to 0.25 mM) in the absence of dithiothreitol, no inhibition is seen in its presence at inhibitor concentrations as high as 200 μg/ml. Against the deoxyribonucleic acid-directed RNA polymerases of
Escherichia coli
and chicken embryo cells, acetylaranotin and 4-(2-propinyloxy)-β-nitrostyrene caused very little inhibition. Only selenocystine significantly inhibited these two enzymes in the absence of reducing agent, but to an extent substantially less than that obtained against the viral enzyme. These results appear to suggest that influenza RNA polymerase is uniquely sensitive to a variety of structurally diverse antiviral compounds as a consequence of their sulfhydryl reactivity—a fact which might aid in the search for and development of more potent chemotherapeutic agents.
Lysis of Enterococcal L-Forms by Phenylethyl Alcohol
Authors: King James R.
Published: June 2012

Enterococcal L-forms were lysed by phenylethanol, as shown by turbidimetric analysis and electron microscopy.
Potentiation of the Antibacterial Effect of Methanamine by Acetohydroxamic Acid
Authors: Musher Daniel M. , Griffith Donald P. , Tyler Michael , Woelfel Alan
Published: June 2012

In vitro testing shows nearly all strains of
Proteus
to be susceptible to methenamine. However, infection by urease-producing bacteria alkalinizes the urine in vivo and prevents generation of formaldehyde, the active metabolite, from methenamine. We have previously shown acetohydroxamic acid (AHA) to be an effective inhibitor of bacterial urease in vitro and in vivo. We now present data obtained by use of static and dynamic in vitro systems, which show that, by preventing urease-induced alkalinization of urine, AHA enables methenamine to exert its antibacterial effect against representative
Proteus
species.
R Factor-Mediated and Chromosomal Resistance to Ampicillin in
Escherichia coli
Authors: Roupas A. , Pitton J. S.
Published: June 2012

Sixty-four ampicillin-resistant strains of
Escherichia coli
were studied. Six characters were examined: (i) resistance to ampicillin, cephalothin, and carbenicillin, (ii) synergy between ampicillin and cloxacillin, (iii) level of β-lactamase activity after osmotic shock, (iv) transferability of ampicillin resistance, (v) immunological characterization of the enzyme, and (vi) determination of substrate profiles. One class of strains was found in which synthesis of β-lactamase is inferred to be plasmid mediated; these strains are highly resistant to ampicillin and carbenicillin, sensitive to cephalothin, do not show synergism between ampicillin and cloxacillin, and reveal a high enzymatic activity after osmotic shock. A second class is formed by strains for which β-lactamase synthesis is inferred to be chromosomal; these strains present a low resistance level to ampicillin, are sensitive to carbenicillin and resistant to cephalothin, show a synergism between ampicillin and cloxacillin, and reveal a very low enzymatic activity after osmotic shock. These characters may be used to differentiate periplasmic and cell-bound β-lactamases.
Properties of Silver Sulfadiazine-Resistant
Enterobacter cloacae
Authors: Rosenkranz Herbert S. , Coward Joe E. , Wlodkowski Theodore J. , Carr Howard S.
Published: June 2012

Two silver sulfadiazine-resistant isolates of
Enterobacter cloacae
obtained in a burns unit where the drug was in use were studied. These strains were resistant to elevated levels of the drug, and they were cross-resistant to silver benzoate, but not to silver nitrate. Growth of the strains in nutritionally poor defined media sensitized them to the inhibitory action of the drug. Exposure of the bacteria to penicillins rendered them susceptible to silver sulfadiazine. The resistant bacteria harbored episomes for resistance to carbenicillin and kanamycin; however, resistance to silver sulfadiazine could not be transferred by these episomes. Twenty-three strains of
E. cloacae
isolated in a general hospital were sensitive to much lower levels of the drug (≤50 μg/ml).
Mechanism of the Antiviral Action of 3-Methyleneoxindole
Authors: Tuli V.
Published: June 2012

The biochemical basis underlying the antiviral action of 3-methyleneoxindole (MO), a plant metabolite, was examined in HeLa cells infected with poliovirus. In the presence of antiviral concentrations of MO, poliovirus-specific ribonucleic acid (RNA) synthesis can proceed normally, and the RNA synthesized under such conditions is infectious. It is suggested that the ability of MO to bind to ribosomes of HeLa cells may underlie the antiviral affect. Data are presented which indicate that poliovirus messenger RNA cannot attach to those ribosomes which already are bound to MO. Consequently, virus-specific polysomes cannot be recovered from infected cells treated with antiviral concentrations of MO. In contrast, antiviral concentrations of MO do not prevent the formation of polysomes in uninfected HeLa cells.
Effect of R-Factor-Mediated Drug-Metabolizing Enzymes on Survival of
Escherichia coli
K-12 in Presence of Ampicillin, Chloramphenicol, or Streptomycin
Authors: Lundbäck Annika , Nordström Kurt
Published: June 2012

Escherichia coli
K-12 carrying the R-factor R1 is resistant to ampicillin, chloramphenicol, and streptomycin. This resistance is due to R-factor-coded enzymes that metabolize the drugs. The effects of these enzymes on the survival of cell populations were studied in the presence of high concentrations of antibiotics. For all three antibiotics there were considerable inoculum effects. For ampicillin and chloramphenicol, the inoculum effect was due to detoxification of the medium, whereas streptomycin was not significantly metabolized. The survival of the population in the presence of streptomycin was due to the presence of resistant mutants. At high concentrations of ampicillin or chloramphenicol, the surviving cells were not mutants. Survival in the presence of ampicillin is presumably due to variations in resistance during the cell division cycle. The rate of acetylation of chloramphenicol decreased with time and was zero after 1 to 2 h. Treatment with high concentrations of chloramphenicol did not cause lysis of the cells but partially opened the outer membrane, causing excretion of β-lactamase.
Alleged Effect of Bile Constituents on Gentamicin Assays
Authors: McDonald D. R. , Waterworth Pamela M.
Published: June 2012

It has been claimed that gentamicin assays on the serum of jaundiced patients give falsely low levels and suggested that the antibiotic in such sera is bound to bile acids and thus is partly inactivated. No evidence of such inactivation has been obtained (i) in the serum of jaundiced patients treated with gentamicin, (ii) in sera with high bilirubin contents to which gentamicin was added, or (iii) when bile or bile acids were added with gentamicin to normal serum.
Susceptibility of
Clostridium ramosum
to Antimicrobial Agents
Authors: Tally Francis P. , Armfield Ann Y. , Dowell V. R. , Kwok Yung-Yuan , Sutter Vera L. , Finegold Sydney M.
Published: June 2012

The susceptibility of 49 strains of
Clostridium ramosum
to 10 antibiotics was determined by agar dilution and disk diffusion tests. Results showed that, among the anaerobes,
C. ramosum
is second only to
Bacteroides fragilis
in its resistance to antimicrobial agents. All strains were susceptible to penicillin, carbenicillin, chloramphenicol, vancomycin, and metronidazole at readily achievable blood levels. Most strains (83%) were susceptible to erythromycin. There was a high level of resistance to clindamycin in 16% of the strains. All isolates were resistant to rifampin and gentamicin, and most were resistant to lincomycin. Assessment of susceptibility by measurement of inhibition zone diameters with disk diffusion tests was not satisfactory.
Comparison and Evaluation of Carbenicillin Disks in Diffusion Susceptibility Testing
Authors: Matsen John M. , Lund Marlys E. , Brooker Doris C.
Published: June 2012

A broad variety of bacterial strains, including 79
Pseudomonas aeruginosa
, were studied in an in vitro evaluation of carbenicillin disk susceptibility testing. Regression analysis with both 50-μg and 100-μg carbenicillin disks was carried out. Organisms having minimal inhibitory concentration values of 100 to 200 μg/ml demonstrated zones of less than 11 mm with the 50-μg disk, resulting in very little opportunity for appropriate discrimination of results. The line of regression for the 50-μg disk intersected the ordinate at a point just above the minimal inhibitory concentration value considered to be the limit of intermediate susceptibility for
Pseudomonas
. These considerations, together with evidence of greater disk content variation in the 50-μg than in the 100-μg disks assayed, considerable manufacturer-to-manufacturer variability with the 50-μg disk, and the more appropriate performance of the 100-μg disk, lead us to conclude that the 100-μg disk better serves the clinical test requirements for this agent than does the 50-μg disk, which is currently the only disk available for laboratory testing.
Alteration of Contractile Function and Calcium Ion Movements in Vascular Smooth Muscle by Gentamicin and Other Aminoglycoside Antibiotics
Authors: Adams H. Richard , Goodman Frank R. , Weiss George B.
Published: June 2012

Experiments were conducted to examine the effects of certain aminoglycoside antibiotics on contractile responses and related calcium ion (Ca
2+
) movements in isolated vascular smooth muscle. Gentamicin, kanamycin, and streptomycin decreased contractile responses produced by norepinephrine, histamine, and high K
+
in rabbit aortic strips. The inhibitory action of these antibiotics on mechanical function was more pronounced when the Ca
2+
concentration of the bathing solution was decreased from 1.5 mM (normal Ca
2+
solution) to 0.05 mM (low Ca
2+
solution). The uptake of radiocalcium (
45
Ca) into the isolated media-intimal layer of rabbit aortae was decreased in a maintained manner by each antibiotic. With gentamicin, the inhibitory effect on
45
Ca uptake was shown to be dependent upon the concentration of gentamicin employed and to be more evident in a 0.1 mM Ca
2+
solution than in a normal Ca
2+
solution. In addition, the rate of
45
Ca efflux from the rabbit aortic media-intimal layer was increased in a sustained manner by gentamicin, streptomycin, and kanamycin. Furthermore, contractile responses induced by high K
+
and norepinephrine in canine carotid arterial strips were inhibited by gentamicin. Present findings indicate that aminoglycoside antibiotics interfere with Ca
2+
-linked events leading to activation of the contractile mechanism of vascular smooth muscle. These in vitro findings may partially explain the occurrence of in vivo cardiovascular depression that has occasionally been observed after the administration of chemically related antimicrobial agents.
Inhibition of Growth of
Mycobacterium smegmatis
and of Cell Wall Synthesis by
d
-Serine
Authors: Yabu Kunihiko , Huempfner Herman R.
Published: June 2012

d
-Serine inhibited the growth of
Mycobacterium smegmatis
and induced the morphological alteration of the bacilli. The growth inhibitory action of
d
-serine was partially reduced by an equimolecular concentration of
d
-alanine. The combination of glycine with
d
-alanine reversed the growth inhibition produced by
d
-serine more than did
d
-alanine alone. In cells cultured in the presence of
d
-serine, the amounts of alanine, diaminopimelic acid, and glycine inserted into the cell wall mucopeptide were reduced, and serine was increased. The intracellular accumulation of a precursor of cell wall mucopeptide was increased by
d
-serine, and this accumulation was reduced by
d
-alanine.
d
-Serine competed with glycine for incorporation into the cell wall mucopeptide. The incorporation of
l
-aspartic acid into diaminopimelic acid residues in the cell wall mucopeptide was markedly inhibited by
d
-serine. Three mutants resistant to
d
-serine were isolated by nitrosoguanidine treatment. In these mutants the effects of
d
-serine on the sites of cell wall mucopeptide synthesis were all reduced. Thus,
d
-serine inhibition of the growth is due to replacement of glycine residues of the cell wall mucopeptide with
d
-serine and inhibition of the cell wall synthesis by blocking the formation of
d
-alanine and diaminopimelic acid.
Rapid Radiometric Method of Testing Susceptibility of Mycobacteria and Slow-Growing Fungi to Antimicrobial Agents
Authors: Benitez Pamela , Medoff Gerald , Kobayashi George S.
Published: June 2012

[
3
H]uracil incorporation into the ribonucleic acid (RNA) of mycobacteria and [
3
H]guanine incorporation into the RNA of fungi were used as measures of cell viability in the presence of several antimicrobial agents. There appeared to be an excellent correlation between traditional susceptibility tests, which required 1 to 4 weeks, and tests of the inhibition of incorporation of RNA precursors, which were completed in 4 to 48 h. The radiometric method may be useful in rapidly determining the susceptibility of slow-growing organisms to antimicrobial agents.
Determination of Plaque Inhibitory Activity of Adenine Arabinoside (9-β-
d
-Arabinofuranosyladenine) for Herpesviruses Using an Adenosine Deaminase Inhibitor
Authors: Bryson Yvonne , Connor James D. , Sweetman Lawrence , Carey Sharen , Stuckey Margaret A. , Buchanan Robert
Published: June 2012

The in vitro susceptibility of type 1 and type 2 strains of
Herpesvirus hominis
to 9-β-
d
-arabinofuranosyladenine (adenine arabinoside, ara-A) was measured in a system where deamination was inhibited. Under these conditions, it was possible to measure the activity of low concentrations of ara-A. It was determined that plaque inhibitory concentration for type 1 viruses was less than 3 μg/ml for all strains tested. The plaque inhibitory concentration for 7 of 10 type 2 strains was also less than 3 μg/ml. The method used identified and controlled the interaction between antiviral agent (ara-A) and the indicator system, human skin fibroblastic cells. Otherwise, metabolism of ara-A resulted in rapid enzymatic degradation and loss of antiviral activity.
Antigen Specific for Bacteria Resistant to Tetracycline
Authors: Boldur Ida , Sompolinsky David
Published: June 2012

Antisera produced against envelope fractions of tetracycline-resistant
Escherichia coli
and supernatant fluid of disrupted cells of tetracycline-resistant
Salmonella typhi
were adsorbed with the corresponding fractions of susceptible cultures. With these sera, cross-reacting antigens were demonstrated in the following fractions obtained from tetracycline-resistant strains: envelopes of
E. coli
, supernatant fluid of
S. typhi
, and envelopes and supernatant fluid of
Pseudomonas aeruginosa
. These antigens were not demonstrable in the corresponding fractions from tetracycline-susceptible strains.
Macromolecule Metabolism and Photosynthetic Functions in Blue-Green Algae Treated with Virginiamycin, an Inhibitor of Protein Synthesis
Authors: Cocito C. , Shilo M.
Published: June 2012

The M component of virginiamycin inhibited growth of
Plectonema boryanum
under both photoautotrophic and heterotrophic conditions. Though the S component of this antibiotic had no apparent activity per se, it enhanced the inhibitory action of its partner. Cells incubated with suitable concentrations of either M or M + S stopped growing and lysed. Loss of the colony-forming capacity occurred quickly in the presence of M + S and slowly in the presence of M alone. Virginiamycin M inhibited protein synthesis in autotrophically and heterotrophically growing
Plectonema
. This effect was very rapid and could be reversed by removing the antibiotic. The S component did not block the incorporation of amino acids into proteins, but prevented the reversibility of the inhibitory effect of M. Virginiamycin M or S did not affect the photosynthetic oxygen development (Hill's reaction) in
Plectonema
. Moreover, carbon dioxide photoassimilation and formation of chlorophyll were inhibited only after an appreciable lag. Deoxyribonucleic acid synthesis was blocked virtually without delay by virginiamycin M. Since virginiamycin inhibited protein synthesis in a similar fashion in the unicellular
Anacystis nidulans
, as well as in the filamentous
P. boryanum
, the mechanism of action of this antibiotic is probably the same in all blue-green algae.
Effect of Chelating Agents on the Susceptibility of Some Strains of Gram-Negative Bacteria to Some Antibacterial Agents
Authors: Haque H. , Russell A. D.
Published: June 2012

The effects of ethylenediaminetetraacetic acid and related chelating agents on the susceptibility of
Pseudomonas aeruginosa
and other strains of gram-negative bacteria to some β-lactam antibiotics and some non-antibiotic antibacterial agents have been studied by two methods: (i) the determination of minimal inhibitory concentrations in the presence and absence of a chelating agent; and (ii) pretreatment with a chelating agent, followed by exposure for up to 120 min at 37 C to a β-lactam drug in a nutrient medium or to the other type of antibacterial agent in a non-nutrient environment. The pretreatment technique gave the more significant results, especially with chlorhexidine, cetrimide, and benzalkonium chloride. Chelating agents that had previously been found to give a low order of activity as measured by effects on bacterial viability nevertheless appeared to induce some changes in the surface layers of the treated organisms, rendering them susceptible to sub-inhibitory concentrations of non-antibiotic drugs.
Cefoxitin and Cephalothin: Antimicrobial Activity, Human Pharmacokinetics, and Toxicology
Authors: Brumfitt William , Kosmidis John , Hamilton-Miller Jeremy M. T. , Gilchrist James N. G.
Published: June 2012

Cefoxitin, a semisynthetic cephamycin, has been compared with the widely used parenteral cephalosporin, cephalothin, in terms of antibacterial activity, human pharmacokinetics, and toxicity. For both compounds, minimal inhibitory concentrations were within the therapeutic range against the 156 gram-positive cocci tested (except group D streptococci), but cephalothin was 8 to 20 times more active. Regarding the 313 gram-negative organisms tested, both antibiotics were of approximately equal activity against cephalothin-susceptible strains, but cefoxitin was outstandingly superior against
Providencia
spp. and indole-producing
Proteus
spp., and markedly better against
Serratia marcescens
and
Bacteroides fragilis
. Against these organisms, cefoxitin but not cephalothin would be expected to be therapeutically valuable. Antibiotic activity levels in the serum and urine of 18 human volunteers after parenteral administration were higher and more prolonged in the case of cefoxitin, which had an average terminal serum half-life of about 45 min and a urinary recovery of about 90%. Cefoxitin was entirely nontoxic and, given intramuscularly, slightly less painful then cephalothin. These preliminary results suggest that cephamycins may prove to be a significant chemotherapeutic advance.
Impaired Penicillin Production in Lysine Regulatory Mutants of
Penicillium chrysogenum
Authors: Masurekar Prakash S. , Demain Arnold L.
Published: June 2012

Lysine-regulatory mutants of
Penicillium chrysogenum
which excrete lysine were found to be deficient in production of penicillin. A revertant recovered the ability to produce penicillin.
Production of Cephalosporin C by
Paecilomyces persicinus
P-10
Authors: Pisano M. A. , Vellozzi E. M.
Published: June 2012

After the growth of
Paecilomyces persicinus
P-10 in a glucose-peptone medium, filtrates were collected and analyzed for antibiotic antivity. Activities against
Salmonella gallinarum
ATCC 3030 and
Alcaligenes faecalis
ATCC 8750 (penicillin N-resistant strain) were obtained. Part of the former activity was readily inactivated by penicillinase. The fraction active against
A. faecalis
was isolated by passage through Amberlite XAD-2 and Amberlite IRA-68. The powder eventually obtained was subjected to paper chromatography followed by bioautography, and the activity obtained corresponded to that of a sample of cephalosporin C. Thin-layer chromatography was also employed to verify the presence of cephalosporin C in the P-10 powder. The active solids were further purified by means of paper chromatography in a solvent system consisting of
n
-butanol-acetic acid-water (60:15:25, vol/vol). The material obtained from this procedure yielded an infrared absorption spectrum identical to that of cephalosporin C. Similarly, the ultraviolet absorption of the purified preparation coincided with that of cephalosporin C. Exposure of the purified solids to cephalosporinase resulted in rapid inactivation of the antibiotic. In addition to penicillin N and cephalosporin C, filtrates of
P. persicinus
P-10 also contained deacetylcephalosporin C, deacetoxycephalosporin C, and cephalosporin P.
Evaluation of Two Standardized Disk Methods for Testing Antimicrobial Susceptibility of
Pseudomonas aeruginosa
and of the
Enterobacteriaceae
Authors: Barry Arthur L. , Effinger Lee J.
Published: June 2012

Two standardized disk diffusion susceptibility testing methods were compared using
Pseudomonas aeruginosa
and members of the
Enterobacteriaceae
. The standard Bauer-Kirby method and the agar overlay method of Barry et al. were compared using carbenicillin (50- and 100-μg disks), gentamicin, polymyxin B, and colistin sulfate. Both methods gave nearly comparable zone sizes with the enteric bacilli. However, with
P. aeruginosa
the agar overlay method gave zones 1 to 2 mm smaller than the Bauer-Kirby method with all drugs except gentamicin. In spite of these small differences, further examination of minimal inhibitory concentration-zone size correlations indicated that the same interpretive zone standards can be applied to either diffusion technique. For testing carbenicillin against
Pseudomonas
sp., 50-μg disks were unsatisfactory, especially with the agar overlay method; 100-μg disks were far superior with both methods.
Effect of Amphotericin B and Clotrimazole on Lymphocyte Stimulation
Authors: Tärnvik Arne , Ånséhn Steffan
Published: June 2012

Human lymphocytes were stimulated in vitro by phytohemagglutinin, concanavalin A, pokeweed mitogen, purified protein derivative-tuberculin, and allogenic cells. The deoxyribonucleic acid synthesis of the lymphocytes was inhibited in increasing degree by 4 to 8 μg of amphotericin B per ml of culture irrespective of lymphocyte stimulant used. The effect of clotrimazole on the deoxyribonucleic acid synthesis varied between experiments with different and also between experiments with the same stimulant. Ten micrograms of clotrimazole per ml was generally inhibiting, whereas in one experiment 2 μg or more per ml inhibited the purified protein derivative-induced deoxyribonucleic acid synthesis. The effects of amphotericin B and clotrimazole were neutralized by serum.
Comparative In Vitro Evaluation of BL-P1654 and Carbenicillin Against
Pseudomonas
Authors: Overturf G. D. , Ressler R. , Wilkins J.
Published: June 2012

Prior investigators have reported a broad gram-negative spectrum and a marked anti-
Pseudomonas
activity in vitro with BL-P1654, 6-[R-alpha-(guanylureido)phenylacetamido]-penicillanic acid. An in vitro comparison of BL-P1654 to carbenicillin was performed against 84 strains of
Pseudomonas
and 39 strains of
Enterobacteriaceae
. Mean minimal inhibitory concentrations in Mueller-Hinton broth of BL-P1654 and carbenicillin were 12.5 and 100 μg/ml, respectively. Bactericidal studies with representative strains of
Pseudomonas
showed a consistent lack of bactericidal activity with BL-P1654. Mean bactericidal concentrations of BL-P1654 and carbenicillin were ≥200 and 100 μg/ml, respectively. The lack of bactericidal activity of BL-P1654 was further substantiated with the “killing curve” technique. Based on these data, BL-P1654 can not be considered a substitute for carbenicillin as the penicillin analogue of choice for
Pseudomonas
infections.
Microbiological Assays and Bioautography of Maytansine and Its Homologues
Authors: Hanka L. J. , Barnett M. S.
Published: June 2012

A quantitative microbiological assay and a bioautography system with
Penicillium avellaneum
UC-4376 was developed for the antitumor drugs maytansine, and its homologues, maytanprine and maytanbutine. The susceptibility of the assay is 1.5 μg/ml.
Effect of R-Factor-Mediated Genes on Some Surface Properties of
Escherichia coli
Authors: Curtis N. A. C. , Richmond M. H.
Published: June 2012

The plasmid RP1 was shown to contain a genetic region (the
irp
region) responsible for influencing the intrinsic resistance of
Escherichia coli
to penicillins but not to cephalosporins. Mutants in which the
irp
genes are inactive were isolated. RP1 carrying functional
irp
genes protected
E. coli
AS19 against lysozyme lysis and also enhanced resistance to actinomycin D, to nalidixic acid, and to rifampin. This plasmid also phenotypically repaired the hypersensitivity to penicillins of strain AS19, and also that of
E. coli envA
mutants. Similar regions were not detected on the plasmids R1 and R55.
Induction Kinetics of β-Lactamase Biosynthesis in
Pseudomonas aeruginosa
Authors: Nordström Kurt , Sykes Richard B.
Published: June 2012

The induction of β-lactamase in
Pseudomonas aeruginosa
1822s was studied using benzylpenicillin as inducer. The specific rate of β-lactamase formation was constant throughout an induction experiment. Above a threshold (20 μg/ml), the specific activity increased linearly with the concentration of the inducer. Removal of the inducer resulted in a rapid cessation of β-lactamase biosynthesis. Inhibition of protein synthesis by starvation for a required amino acid or by the addition of chloramphenicol also led to an instantaneous arrest in enzyme formation. In the absence of inducer, a basal β-lactamase activity was formed. The basal and the induced enzymes seem to be identical since they had the same substrate profile, electrophoretic mobility, and molecular weight. In all these respects, induction of β-lactamase in
Pseudomonas aeruginosa
is analogous to induction of the
lac
operon in
Escherichia coli
. However, there was a long, concentration-dependent lag before β-lactamase was induced. This can be explained by the outer penetration barrier decreasing the rate of inducer uptake. The lag was significantly shorter for lysozyme-ethylenediaminetetraacetic acid-produced spheroplasts than for intact cells. Induction was obtained with all β-lactam antibiotics tested, but not with other agents affecting the cell envelope.
Characterization of the Binding of Amphotericin B to
Saccharomyces cerevisiae
and Relationship to the Antifungal Effects
Authors: Kotler-Brajtburg Janina , Medoff Gerald , Schlessinger David , Kobayashi George S.
Published: June 2012

Based on the enhanced fluorescence of amphotericin B in acid solutions, a quantitative assay for this polyene antibiotic has been developed that is sensitive and linear in the range of 0.1 to 10.0 μM. The binding of amphotericin B to
Saccharomyces cerevisiae
was assayed under various conditions as the amount bound to cells in a dialysis chamber or after centrifugation. Two types of binding were defined: weak, reversible binding occurred at 0 C or higher temperatures and even in the presence of inhibitors of energy metabolism, whereas strong, irreversible binding did not occur at 0 C and was inhibited when energy metabolism was blocked. Only strong binding was correlated with cell killing. Weak binding probably involves the outer layer of the membrane; strong binding probably requires disruption of hydrophobic regions of the cell membrane.
Active Insolubilized Antibiotics Based on Cellulose-Metal Chelates
Authors: Kennedy J. F. , Barker S. A. , Zamir A.
Published: June 2012

Cellulose was converted into a more reactive form by chelation with the transition metals titanium
III
, iron
III
, tin
IV
, vanadium
III
, and zirconium
IV
. The remaining unsubstituted ligands of the transition metal ions were found to be amenable to replacement by electron-donating groups of antibiotic molecules. Ampicillin, gentamicin, kanamycin, neomycin, paromomycin, polymyxin B, and streptomycin were used as antibacterial antibiotics, and amphotericin B and natamycin were used as antifungal antibiotics. Antibacterial activity of the products was tested against two gram-positive and two gram-negative bacteria, and antifungal activity was tested against four fungi. That the antibacterial antibiotics had complexed with the cellulose-metal chelates was demonstrated in that the product cellulose-metal-antibiotic chelates exhibited antibiotic activities whereas the metal chelates of cellulose themselves were inactive. Of 140 tests conducted, cellulose-metal-antibiotic chelates were active in 102 cases. Since the antibiotic derivatives were water insoluble and in fact retain some of the antibacterial activities of the parent compounds, the chelation method provides a facile way of rendering cellulose surfaces, etc., resistant to microbial attack over and above that degree of protection afforded by noncovalent adsorption of the antibiotic to cellulose itself. The underlying principles of the chelation reactions involved are discussed in detail.
In Vitro Susceptibility of
Haemophilus influenzae
to Trimethoprim-Sulfamethoxazole
Authors: Kirven Linda A. , Thornsberry Clyde
Published: June 2012

Thirty-four strains of
Haemophilus influenzae
(20 ampicillin sensitive and 14 ampicillin resistant), mostly type b isolates from cerebrospinal fluid or blood, were tested for susceptibility to a combination of trimethoprim-sulfamethoxazole (TMP-SMZ) in a ratio of 1 part TMP to 19 parts SMZ. All strains were very susceptible to the TMP-SMZ combination, with minimal inhibitory concentrations ranging from 0.007–0.14 to 0.06–1.18 μg of TMP-SMZ per ml. There was little difference in the susceptibility of the ampicillin-sensitive and ampicillin-resistant strains to TMP-SMZ.