bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycobacterium chelonei
Infection: Successful Treatment Based on a Radiometric Susceptibility Test
Authors: Arroyo Julio , Medoff Gerald
Published: June 2012

A patient with
Mycobacterium chelonei
infection was treated with erythromycin stearate and streptomycin. The choice of antibiotics was based on a rapid radiometric susceptibility test developed in our laboratory.
Inhibition of Herpes Simplex Virus Strains Isolated from Herpetic Keratitis by Polyinosinic Acid-Polycytidylic Acid
Authors: Smetana Ofira , Eylan Emanuel , Weinberg Miriam
Published: June 2012

Fifty strains of herpes simplex virus, isolated from patients with herpetic keratitis, were examined in vitro for susceptibility to polyinosinic acid-polycytidylic acid [poly(I:C)] in the presence of a constant concentration of diethylaminoethyl-dextran. The minimal inhibitory concentration of poly(I:C) for 44 of these strains ranged from 0.0001 to 0.1 μg/ml; for the remaining six strains, the minimal inhibitory concentration stood at 1 to 2 μg/ml. Fifteen isolates from primary infections were more susceptible to poly(I:C) than 35 isolates from recurrent infections. Isolates acquired at different points of a given clinical episode showed similar susceptibilities to poly(I:C). In two patients, isolates from consecutive recurrences of infection exhibited reduced susceptibilities. The implications of the above observations for the therapeutic use of poly(I:C) are discussed.
Inducible Resistance to
d
-Cycloserine in
Bacillus subtilis
168
Authors: Clark Virginia L. , Young Frank E.
Published: June 2012

Resistance to
d
-cycloserine could be induced in
Bacillus subtilis
168 by sublethal concentrations of
d
-cycloserine. Sensitivity to the antibiotic could be regained by growth in the absence of
d
-cycloserine. The bactericidal activity of
d
-cycloserine apparently was not altered by resistant cells, and peptidoglycan synthesis was still inhibited by
d
-cycloserine in resistant cells. The
d
-cycloserine resistance apparently resulted from a decreased uptake of the antibiotic. The decrease in
d
-cycloserine transport could be prevented by simultaneous treatment of the cells with rifampin and
d
-cycloserine.
d
-Cycloserine was transported by the same system as glycine in
B. subtilis
.
d
-Cycloserine was able to exchange for intracellular glycine in both sensitive and resistant cells, suggesting that
d
-cycloserine is not excluded from the cell in resistant cultures.
Penetration of Cefazolin into Pleural Fluid
Authors: Cole Donald R. , Pung Juanito
Published: June 2012

Single doses of cefazolin, 500 mg intramuscularly and 1 g intravenously, were administered to 16 patients having lung pathology who were scheduled for thoracic fluid aspiration. Pleural fluid and serum samples were taken at intervals of 30 to 240 min for determination of cefazolin levels. The levels obtained were variable; however, the levels of cefazolin in pleural fluid generally exceeded the reported minimal inhibitory concentration values for
Staphylococcus pneumoniae
and
Staphylococcus
, and group A beta-hemolytic streptococcus. In addition, the pleural fluid levels exceeded the minimal inhibitory concentration for cefazolin against most of the
Klebsiella
and
Haemophilus influenzae
strains. These data show that cefazolin, despite its comparative high protein binding, produces levels in the pleural fluid capable of inhibiting the organisms commonly found in respiratory tract infections.
Drug Resistance in Group D Streptococci of Clinical and Nonclinical Origin: Prevalence, Transferability, and Plasmid Properties
Authors: Van Embden J. D. A. , Engel H. W. B. , Van Klingeren B.
Published: June 2012

Group D streptococci isolated from clinical specimens and from sewage were investigated with regard to resistance to tetracycline (Tc), erythromycin (Em), and chloramphenicol (Cm). The median values of the percentages of resistant strains from sewage were: for Tc, 14%; for Em, 2.8%; and for Cm, 0.1%. For the recent isolates of clinical origin, resistance percentages found were 58% for Tc, 12% for Em, and 14% for Cm, and, in comparison to clinical isolates from 1964, the incidence of drug resistance slightly increased. In strains of both sources, the drug resistance was often found to be transferable to another group D streptococcus, probably by conjugation. Two strains were able to transfer their Em resistance to a streptococcus strain of group B. No transfer of drug resistance to a group A streptococcus and
Escherichia coli
was observed. All beta-hemolytic streptococci were also bacteriocinogenic, and frequently these properties were found to be transferable. The function, size, and base composition of the plasmids of two drug-resistant
Streptococcus faecalis
strains were investigated; strain M439 harbors at least two conjugative plasmids: pRI401, molecular weight 30 × 10
6
, coding for Tc resistance, and pRI402, molecular weight 41 × 10
6
, coding for Em resistance. Strain M403 carries one single conjugative plasmid species, coding for Tc resistance. The molecular weight of this plasmid, pRI404, was 37 × 10
6
. The guanine plus cytosine content of these plasmids was 35 to 36%.
Mechanism of Accumulation of the Antitumor Protein Antibiotic Neocarzinostatin in Bladder Tissue: Intravenous Administration, Urinary Excretion, and Absorption into Bladder Tissue
Authors: Maeda Hiroshi , Sakamoto Sadaaki , Ogata Jiro
Published: June 2012

Some aspects of the absorption, distribution, and excretion of neocarzinostatin (NCS), a proteinous antitumor antibiotic, were studied in rabbits. NCS was given intravenously (i.v.) via the auricular vein, or [
14
C]NCS was instilled directly into the cavity of the bladder by tubing. In both groups, ureterostomy was performed, so that the drug excreted in the urine did not pass through the bladder. The results showed extremely rapid renal clearance; namely, two-thirds of the total recovered was excreted in the first 5 min. It was also shown that drug infused into the bladder cavity could be recovered in urine from the ureterostomized ureter. Also, the level of biological activity of NCS in bladder tissues after i.v. administration is significantly lower when ureterostomy is performed. Thus, evidence is presented for the absorption of NCS into bladder tissue from the lumen of the bladder. The high levels of NCS in bladder tissue are due to this effect as well as to accumulation via the iliac artery. These data should encourage further trials of NCS in bladder cancer. A study of urine containing NCS derived from i.v. administration showed an increase in antibacterial activity upon incubation, followed by a decrease. These effects are probably due to proteolysis, as shown by the appearance of a low-molecular-weight fragment and by the absence of such an increase in the presence of inhibitors of proteolysis.
Inhibition of Influenza Virus Ribonucleic Acid Polymerase by Ribavirin Triphosphate
Authors: Eriksson Bertil , Helgstrand Erik , Johansson Nils Gunnar , Larsson Alf , Misiorny Alfons , Noren Jan Olof , Philipson Lennart , Stenberg Kjell , Stening Goran , Stridh Stig , Öberg Bo
Published: June 2012

Ribavirin 5′-triphosphate (RTP), derived from the broad-spectrum antiviral compound ribavirin (Virazole), can selectively inhibit influenza virus ribonucleic acid polymerase in a cell-free assay. Ribavirin and its 5′-monophosphate have no effect on the polymerase. The inhibition is competitive with respect to adenosine 5′-triphosphate and guanosine 5′-triphosphate. RTP also inhibits ApG- and GpC-stimulated influenza virus ribonucleic acid polymerase. Since ribavirin is phosphorylated in the cell, the inhibition of influenza multiplication in the cell may also be caused by RTP.
Comparation Interferon-Inducing and Antiviral Properties of 2-Amino-5-Bromo-6-Methyl-4-Pyrimidinol (U-25,166), Tilorone Hydrochloride, and Polyinosinic-Polycytidylic Acid
Authors: Stringfellow Dale A.
Published: June 2012

2-Amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166), polyinosinic acid-polycytidylic acid [poly(I:C)], and tilorone HCl induced high levels of serum interferon in mice. Each consequently protected mice against infection with several viruses. After daily injection of inducer, mice developed a reduced interferon response (hyporeactivity) to each compound. However, hyporeactivity developed more slowly to U-25,166 and poly(I:C) than to tilorone HCl. After onset of hyporeactivity, 5 to 6 days without each inducer were required before normal serum interferon levels could be stimulated. Animals also developed a hyporeactive state as a consequence of Semliki Forest or encephalomyocarditis virus infections. By day 2 of either infection, mice had a suppressed interferon response to tilorone HCl, but remains responsive to poly(I:C) or U-25,166 until day 4. In vivo, poly(I:C) stimulated interferon production in a variety of cells and organs, whereas the tilorone HCl and U-25,166 responses involved a nonlymphoid component of the reticuloendothelial system. In vitro, poly(I:C) induced interferon in a variety of murine cells, U-25,166 was active in murine thymus and spleen organ cultures, and tilorone was inactive. These data indicate that U-25,166 is an interesting low-molecular-weight interferon inducer.
Evaluation of Three Newer Methods for Investigating Protein Interactions of Penicillin G
Authors: Peterson Lancer R. , Gerding Dale N. , Zinneman Horace H. , Moore Barbara M.
Published: June 2012

The interaction of penicillin G with human serum proteins was evaluated by three different techniques: rate of dialysis, cross-linked dextran exclusion, and ultracentrifugation. The rate-of-dialysis technique demonstrated that penicillin G binding to serum was immediate but incompletely reversible. Cross-linked dextran adsorbed or trapped significant amounts of penicillin G, necessitating correction factors of more than 10%. Ultracentrifugation was found to be the most reliable method for quantitative protein-binding determinations of penicillins.
Lytic Effect of Mycobacillin and Its Derivatives on Erythrocytes
Authors: Banerjee P. C.
Published: June 2012

Mycobacillin as well as its
O
-acetyl (tyrosyl and seryl) and ester derivatives is known to have antifungal activity. The antibiotic also possesses hemolytic activity. This latter property is not appreciably altered by partial or complete esterification of its free carboxyl groups. On the other hand, acetylation of the molecule at the two tyrosyl hydroxyl groups nullifies selectively the hemolytic activity.
Antimicrobial Activity of Several Antibiotics and a Sulfonamide Against
Chlamydia trachomatis
Organisms in Cell Culture
Authors: Kuo Cho-Chou , Wang San-Pin , Grayston J. Thomas
Published: June 2012

Minimum inhibitory concentrations of several antibiotics and a sulfonamide for growth of the 15 known immunotypes of
Chlamydia trachomatis
were determined in HeLa 229 cell cultures. The concentrations for complete inhibition of infectious-organism production were (per milliliter): tetracycline, 0.02 to 0.5 μg; rosamicin, 0.05 to 0.25 μg; erythromycin, 0.1 to 0.5 μg; chloramphenicol, 10 μg; penicillin, 0.02 to 50 U; ampicillin, 0.1 to 50 μg; and sulfisoxazole, 2 to 200 μg. The same concentrations of tetracycline, rosamicin, erythromycin, and chloramphenicol were sufficient to inhibit
C. trachomatis
inclusion formation. An increased concentration of sulfisoxazole was often needed to inhibit inclusion formation. Penicillin at 100 U/ml and ampicillin at 100 μg/ml failed to completely inhibit inclusion formation.
In Vitro Uptake of Gentamicin by Rat Renal Cortical Tissue
Authors: Hsu Chen H. , Kurtz Theodore W. , Weller John M.
Published: June 2012

The mechanism of gentamicin uptake in vitro by renal cortical slices of rat kidney was investigated. The cortical-slice-uptake ratio of gentamicin concentration in 1.0 g of tissue water to that of 1.0 ml of incubation medium (SW/M) was 1.44 ± 0.04. The uptake of gentamicin was inhibited by 2 × 10
−5
M dinitrophenol (SW/M = 1.03 ± 0.04) and by anoxia (SW/M = 1.01 ± 0.04). The results indicate that aerobic phosphorylation is required to transport gentamicin into the cells. The uptake of
p
-aminohippurate and tetraethylammonium chloride by renal cortical slices was not affected by gentamicin.
Transferable Plasmids Mediating Multiple-Antibiotic Resistance in
Streptococcus faecalis
subsp.
liquefaciens
Authors: Marder H. P. , Kayser F. H.
Published: June 2012

In strain HK187 (
Streptococcus faecalis
subsp.
liquefaciens
) four plasmids were isolated. The molecular weights, as analyzed in neutral sucrose gradients and by electron microscopy, were found to be about 36 × 10
6
, 31 × 10
6
, 26 × 10
6
, and 4 × 10
6
. Plasmid 3, also designated pFK14, with a molecular weight of 26 × 10
6
, was found to be responsible for resistance to chloramphenicol and erythromycin and also for high-level resistance to streptomycin and lincomycin. In mixed cultures these four resistances could be transferred with high frequency to a plasmid-free recipient,
S. faecalis
strain JH2-2.
Inhibition of
Clostridium botulinum
by 5-Nitrothiazoles
Authors: Dymicky M. , Huhtanen C. N. , Wasserman A. E.
Published: June 2012

A number of 5-nitrothiazoles with various substituents in the 2-position were tested for inhibition of
Clostridium botulinum
in a culture medium. Thiazole itself or 2-bromo- or 2-methylthiazole at 30 μg/ml did not inhibit the organism. An amino group in the 2-position of thiazole inhibited at 10 μg/ml. Substitution of a nitro group in the 5-position of 2-aminothiazole increased the inhibitory level to 0.12 μg/ml; acetyl-, propionyl-, or butyroyl-2-amino-5-nitrothiazole inhibited at 0.04 μg/ml. Benzoyl-2-amino-5-nitrothiazole inhibited at 0.16 μg/ml; this increased to 0.01 μg/ml when the benzoyl group carried a nitro group in the
m
- or
p
-position; a nitro group in the
o
-position, on the other hand, inhibited at 0.04 μg/ml. Unsaturated aliphatic acyls decreased inhibition. The greatest activity was exhibited by 2-nonanoyl- and 2-lauroylamides, with minimum inhibitory concentrations of 0.005 and 0.0025 μg/ml, respectively.
Host Function Specified by
Bacillus pumilus
Plasmid pPL7065
Authors: Lovett P. S. , Duvall E. J. , Bramucci M. G. , Taylor R.
Published: June 2012

Plasmid pPL7065 (∼4.7 × 10
6
daltons; ∼20 copies per chromosome) determines the production of, and immunity or resistance to, a killing activity in strains of
Bacillus pumilus
. Plasmid pPL7065 is compatible with plasmid pPL576 (∼28 × 10
6
daltons; ∼2 copies per chromosome).
In-Use Evaluation of a Prediluted Quantitative Antibiotic Susceptibility Test Device
Authors: Tilton Richard C. , Isenberg Henry D.
Published: June 2012

An antibiotic susceptibility test (AST) device is described. Minimum inhibitory concentration results on 1,294 clinical isolates with seven antibiotics were rapid, reliable, and reproducible. Agreement with the disk diffusion test was 90%. Interlaboratory agreement for the AST was 94%. The AST provides minimum inhibitory concentration capability without the necessity of prior weighing and dilution of antibiotics.
In Vitro Studies with Cefaclor, a New Oral Cephalosporin
Authors: Sanders Christine C.
Published: June 2012

In vitro studies were performed to evaluate the activity of cefaclor in comparison with cephalexin against 180 clinical isolates. Broth dilution susceptibility tests showed cefaclor to be 4- to 16-fold more active than cephalexin against
Streptococcus pneumoniae, Haemophilus influenzae
, and cephalothin-susceptible
Enterobacteriaceae
. Neither drug was highly active against cephalothin-resistant
Enterobacteriaceae
or methicillin-resistant
Staphylococcus aureus
. Cefaclor zones with 30-μg disks were generally larger than cephalexin zones, 4 mm larger than cephalothin zones against
Enterobacteriaceae
, and 6 mm smaller than cephalothin zones against
S. aureus
. Quantitative kill curves indicated that killing by both cefaclor and cephalexin was slow and often incomplete over a 24-h period. Cefaclor-induced filamentation of gram-negative bacilli was not as extensive as that produced by cephalexin, and some spherule formation did occur. However, cefaclor was significantly more unstable in solution than cephalexin, with a half-life of less than 6 h at 37°C. Thus, results obtained in tests after prolonged incubation may not provide an accurate measure of cefaclor's activity.
Double-Blind Evaluation of Oral Ribavirin (Virazole) in Experimental Influenza A Virus Infection in Volunteers
Authors: Magnussen C. Richard , Douglas R. Gordon , Betts Robert F. , Roth Frieda K. , Meagher Mary Pat
Published: June 2012

The prophylactic effectiveness of oral administration of ribavirin (1-β-
d
-ribofuranosyl-1,2,4-triazole-3-carboxamide) against experimentally induced influenza A infection was evaluated in a double-blind clinical trial in normal volunteers. Fourteen men received ribavirin capsules (1,000 mg/day in four divided doses) and 15 other men received identical-appearing placebo capsules beginning 6 h after the intranasal inoculation of 3.4 log
10
50% tissue culture infectious doses of influenza virus A/Victoria/3/75 H3N2 and continuing for 5 days after challenge. The total number of moderate-to-severe symptom scores and the total number of temperatures ≥100°F (37.8°C) were significantly lower in the ribavirin group compared with the placebo group. The mean quantity of virus shed in nasal wash specimens and the total number of days that there were viral titers greater than 1.0 log
10
50% tissue culture infectious doses per ml were significantly greater in the placebo group. There was no difference between the frequencies of virus isolated or the antibody responses in the two groups. Therefore, prophylactic ribavirin ameliorated symptoms and fever indicative of moderate-to-severe illness, but had no effect on the manifestations of mild illness in response to influenza A challenge. A transient rise in total serum bilirubin occurred in 29% of the ribavirin-treated volunteers and in none of the placebo-treated volunteers.
Effect of Aminoglycosides on the Chemotactic Response of Human Polymorphonuclear Leukocytes
Authors: Goodhart Glenn L.
Published: June 2012

Leukocyte chemotaxis was inhibited 9.6% compared with control in the presence of 10 μg of gentamicin per ml and 10.5% when exposed to 20 μg of amikacin per ml. However, cells incubated with an injectable form of gentamicin, containing preservatives, were inhibited an additional 25.8% relative to cells incubated with pure gentamicin.
Comparison of In Vitro Antibacterial Activity of Three Oral Cephalosporins: Cefaclor, Cephalexin, and Cephradine
Authors: Silver Michael S. , Counts George W. , Zeleznik Dolores , Turck Marvin
Published: June 2012

Cefaclor, a new oral cephalosporin, was compared in vitro with cephalexin and cephradine against 233 organisms. Evaluations were performed in Mueller-Hinton and nutrient broth and agar using two inoculum sizes. In agar, cefaclor had greater antibacterial activity than either cephalexin or cephradine against isolates of
Escherichia coli, Proteus mirabilis, Staphylococcus aureus, Klebsiella pneumoniae
, and
Salmonella typhi
. All three drugs were relatively inactive against isolates of enterococci,
Enterobacter
species, and indole-positive
Proteus
. Cefaclor, however, did exhibit the greatest activity of the three antibiotics against these organisms. Although there was wide variability with respect to test parameters, the broth results generally paralleled the agar results. In nutrient broth a clear separation of the results with these three cephalosporins was seen with
K. pneumoniae, E. coli
, and
S. typhi
. Cefaclor was the most active, cephalexin had intermediate activity, and cephradine was the least active. From the data obtained in this in vitro study, it can be concluded that cefaclor, which has a substituted chloro group attached to the molecule, had increased antibacterial activity over cephalexin and cephradine. Comparative clinical trials with cefaclor will determine whether the differences outlined above are of clinical significance.
Polymyxin B and Rifampin: New Regimen for Multiresistant
Serratia marcescens
Infections
Authors: Ostenson R. C. , Fields B. T. , Nolan C. M.
Published: June 2012

Polymyxin B and rifampin were given to 12 patients with multi-drug-resistant nosocomial
Serratia marcescens
infections. Eight cures were achieved; drug hepatotoxicity occurred once; one fatal suprainfection was encountered; and two patients died during therapy of causes related to severe underlying illnesses. Polymyxin B and rifampin were uniformly synergistic in vitro against the infecting strains and against 40 additional clinical isolates of
S. marcescens
.
Mechanism of Action of EM 49, Membrane-Active Peptide Antibiotic
Authors: Rosenthal Ken S. , Ferguson Rod A. , Storm Dan R.
Published: June 2012

EM 49 (recently renamed octapeptin) is a membrane-active peptide antibiotic that has been reported to affect the structure of bacterial membranes (K. S. Rosenthal, P. E. Swanson, and D. R. Storm, Biochemistry
15:
5783–5792, 1976). In this study, it is shown that the effects of EM 49 on bacterial metabolism are similar to those of uncouplers of oxidative phosphorylation. EM 49 stimulated bacterial respiration within a narrow concentration range corresponding to minimum inhibitory concentrations and inhibited respiration at concentrations comparable to minimum biocidal concentrations. In addition, the peptide increased membrane proton permeability and lowered the adenosine 5′-triphosphate pool size. Parallel studies done with the related antibiotic polymyxin B demonstrated that the two peptides differed considerably in their effects on bacterial respiration. In contrast to EM 49, polymyxin B did not stimulate respiration at any concentration. It is proposed that the primary action of EM 49 is to disrupt the selective ion permeability of the cytoplasmic membrane, thereby relaxing the membrane potential.
Antibiotic Susceptibility of
Chlamydia trachomatis
Authors: Blackman H. Jane , Yoneda Chieko , Dawson Chandler R. , Schachter Julius
Published: June 2012

The antibiotic susceptibility of
Chlamydia trachomatis
isolates was determined in a tissue culture system. Representatives of all currently recognized serotypes of trachoma-inclusion conjunctivitis agents were tested. Tetracycline and erythromycin yielded similar results, with 1.0 μg/ml preventing chlamydial replication. Rifampin was the most active antibiotic, with 0.25 μg/ml completely suppressing inclusion formation of all strains. Fifty percent end points were usually achieved at one-fourth to one-eighth the 100% suppression level. Penicillin was not as effective, and the assays were often irregular. Antibiotic susceptibility of these chlamydiae was essentially the same, regardless of serotype, anatomic site infected, geographic origin, or antibiotic use in the community.
Penetration of Cefamandole, Cephalothin, and Desacetylcephalothin into Fibrin Clots
Authors: Bergeron Michel G. , Nguyen Bach M. , Trottier Sylvie , Gauvreau Léo
Published: June 2012

The conversion of cephalothin into a less active metabolite (desacetylcephalothin) might influence its distribution in tissues. An experimental rabbit model devised to determine concentrations of antibiotics in subcutaneous fibrin clots was used in this study. Groups of five to six animals received 100-mg/kg intravenous injections of either cefamandole or cephalothin. One hour after the injection, the concentration of cefamandole in serum was 20 times higher than that of cephalothin. Whereas cephalothin was undetectable at 4 h, cefamandole was still detectable at the end of the experiment. The half-lives of cephalothin and cefamandole in serum were 16 and 27 min, respectively. The concentration of cefamandole found in fibrin clots was severalfold higher than that of cephalothin. The half-life of cefamandole in clots (81 min) was superior to that of cephalothin (38 min). Although concentrations of both antibiotics were higher in serum than in clots at 1 h, the concentrations of these drugs in the clots persisted at higher levels throughout the next 5 h of the experiment. The extent of binding of cefamandole (87%) to rabbit serum was greater than that of cephalothin (50%). At least 55% of cephalothin was metabolized in vivo into its less active metabolite desacetylcephalothin. This metabolite was found in higher proportion in the serum (75%) than in the clots (55%). Whereas only 12% of the free (unbound) cephalothin reached the clots, 78% of the free cefamandole was found in the clots. This lower level of penetration of unbound cephalothin might be explained by the short half-life of this antibiotic, not permitting equilibrium to occur.
In Vitro Activity of Antimicrobial Agents on Legionnaires Disease Bacterium
Authors: Thornsberry Clyde , Baker C. N. , Kirven L. A.
Published: June 2012

Six isolates of Legionnaires disease bacteria were tested for their susceptibility to 22 antimicrobial agents. The most active agent was rifampin (minimal inhibitory concentration, ≤0.01 μg/ml). On the basis of minimal inhibitory concentration breakpoints that have been used to categorize susceptibility for most of these drugs, the organisms were susceptible to rifampin, cefoxitin, erythromycin, the aminoglycosides, minocycline and doxycycline, chloramphenicol, ampicillin, penicillin G, carbenicillin, colistin, and sulfamethoxazole-trimethoprim (19:1 ratio); sensitive to intermediate in susceptibility to tetracycline, methicillin, cefamandole, cephalothin, and clindamycin; and resistant to vancomycin. More clinical data must be obtained before an optimal therapeutic regimen can be recommended.
Physiological Conditions Affecting
Staphylococcus aureus
Susceptibility to Staphylococcin 1580
Authors: Weerkamp A. , Vogels G. D.
Published: June 2012

Loss of salt tolerance, irreversible loss of viability, inhibition of
l
-glutamic acid uptake and effects on the high energy state of the membrane were used as parameters to measure the injury induced by staphylococcin 1580, a bacteriocin of
Staphylococcus epidermidis
, in susceptible cells of
Staphylococcus aureus
Oxford 209P. A small part of a growing cell population appeared to be temporarily resistant to the bacteriocin, and the cells were arrested in this stage when suspended in buffer. The proportion of susceptible cells may rapidly shift during exponential growth, apparently concomitantly with a change in cell metabolism. Glucose- and pyruvate-grown cells were equally susceptible to salts after staphylococcin treatment. Only in pyruvate-grown cells was amino acid uptake strongly inhibited, and the membrane potential was abolished after a short lag time. Also, irreversible killing was more distinct in pyruvate-grown cells. The proton gradient across the cell membrane was only slightly disturbed in both types of cells. Specific inhibitors of the energy metabolism revealed that the high energy state of the membrane was largely supported by hydrolysis of adenosine 5′-triphosphate in glucose-grown cells, whereas the oxidative input through electron transport appeared to be relatively more important in pyruvate-grown cells. Staphylococcin 1580 affected primarily the oxidative energy metabolism, although electron transport is not inhibited. Below a distinct incubation temperature cells were completely resistant to the action of the bacteriocin. Varying the growth temperature had only a slight effect on the transition temperature, but growth in the presence of Tween 80, which greatly enhanced the proportion of unsaturated fatty acids, decreased the transition temperature.
Mechanistic Studies of Polyene Enhancement of Interferon Production by Polyriboinosinic-Polyribocytidylic Acid
Authors: Borden Ernest C. , Booth Bruce W. , Leonhardt Peggy H.
Published: June 2012

The production of interferon by polyriboinosinic-polyribocytidylic acid [poly(I) · poly(C)] and poly(I) · poly(C)-diethylaminoethyl-dextran in L929 cells was enhanced from 10 to 100 times by polyene macrolides, including amphotericin B (AmB), AmB methyl ester, nystatin, and filipin. AmB and its water-soluble methyl ester were the most effective; retinol, a nonmacrolide polyene, was ineffective. Interferon induction by Newcastle disease virus was not enhanced by AmB. The kinetics of interferon production were not markedly altered by AmB. Polyenes and poly(I) · poly(C)-diethylaminoethyl-dextran did not need to be present on cells simultaneously to enhance interferon production. Pretreatment with polyenes was as effective as simultaneous addition. Even treatment of washed cells, several hours after removal of poly(I) · poly(C)-diethylaminoethyl-dextran, resulted in enhancement of interferon production. AmB did not appear to form a macromolecular complex with poly(I) · poly(C) in that neither the ultraviolet absorption spectrum nor the melting point of poly(I) · poly(C) was altered by mixing with AmB. Isotopic studies indicated that AmB did not enhance binding of poly(I) · poly(C) to cells. Since the macrolide polyenes have been demonstrated to bind to cell membrane sterols with subsequent alterations in membrane permeability barriers, they may enhance interferon production by increasing cell penetration of poly(I) · poly(C).
Partial Characterization of a Beta-Lactamase from
Vibrio parahaemolyticus
by a New Automated Microiodometric Technique
Authors: DeBell Robert M. , Hickey Thomas M. , Uddin David E.
Published: June 2012

A number of characteristics were determined with a new automated method for a partially purified β-lactamase from
Vibrio parahaemolyticus
. The enzyme had a molecular weight of 28,000 by gel filtration, a pH optimum between 6.5 and 7.0, and a temperature optimum at 36°C. With penicillin G as the substrate, the

K
m

value for the β-lactamase was 54.4 μM. The β-lactamase was inhibited by cloxacillin but not by
p
-chloromercuribenzoate. The enzyme was similar but not identical to β-lactamases from gram-negative, “nonhalophilic” organisms described by other workers. The microiodometric assay to measure β-lactamase activity was automated with the use of a centrifugal analyzer that permitted 14 simultaneous determinations. Within-run precision was tested by putting the same reaction mixture in each well, and the coefficient of variation was only about 3%. Four extracts from different strains of halophilic vibrios were used to demonstrate that reaction rates were linear with enzyme concentration. The correlation coefficient of activity by the automated method with activity by the spectrophotometric method was 0.9721, demonstrating that the methods compared favorably with each other. The automated method greatly facilitated the characterization of the β-lactamase.
Netilmicin: Clinical Efficacy, Tolerance, and Toxicity
Authors: Panwalker Anand P. , Malow James B. , Zimelis Victoria M. , Jackson George G.
Published: June 2012

Netilmicin, a new aminoglycoside antibiotic, has increased in vitro bactericidal activity against many strains of
Enterobacteriaceae
as compared to other aminoglycosides. It is a poor substrate for some of the common gentamicin-inactivating enzymes, and it has minimal toxicity in experimental animals. In 27 hospitalized patients, clinical cure was achieved in all, and the initial infecting organism persisted in only one. Therapeutic serum and urine levels were easily obtained in most patients. No ototoxicity was observed in two patients whose treatment required inordinately high serum levels and in whom other risk factors were present. Ototoxicity in 1 of 21 patients studied was unilateral, partially reversible, and not associated with high serum levels. Although nephrotoxicity occurred in 4 of 25 patients (16%), other host factors could have accounted for the toxicity in two patients. A new observation, not noted with other aminoglycoside antibiotics, was the elevation of serum alkaline phosphatase in 43% of the patients studied.
Outbreak of Multiply Drug-Resistant
Proteus mirabilis
Originating in a Surgical Intensive Care Unit: In Vitro Susceptibility Pattern
Authors: Yoshikawa Thomas T. , Shibata Sharon A. , Chow Anthony W. , Guze Lucien B.
Published: June 2012

A multiply drug-resistant strain of
Proteus mirabilis
was isolated from 14 patients on a surgical service. Antimicrobial susceptibility studies demonstrated that the organism was highly resistant to numerous antibiotics, including gentamicin, tobramycin, and sisomicin. The organism was susceptible in vitro to amikacin but had low-level resistance to netilmicin. In vitro susceptibility studies with combinations of cephalothin with netilmicin and trimethoprim with sulfamethoxazole showed these drugs to be synergistic. Other drug combinations failed to act synergistically.
Comparison of Ticarcillin and Carbenicillin Activity Against Random and Select Populations of
Pseudomonas aeruginosa
Authors: Prior Richard B. , Fass Robert J.
Published: June 2012

The in vitro activities of ticarcillin (T) and carbenicillin (C) against 253 strains of
Pseudomonas aeruginosa
(108 randomly selected clinical isolates and 145 isolates determined to be C resistant by 10 referring hospitals) were evaluated using both broth microdilution and disk diffusion techniques. T activity was usually twofold or greater than C activity for individual strains in both sample populations. The minimal inhibitory concentration (MIC) values of T and C were ≤0.4 to >400 (median, 25) and 0.8 to >400 (median, 50) μg/ml, respectively, for the random sample and 1.6 to >400 (median, 50) and 12.5 to >400 (median, 200) μg/ml, respectively, for the select sample. For predicting susceptibility (MIC, ≤50 μg of T and ≤100 μg of C per ml), 75-μg T and 100-μg C disks were equivalent in accuracy for the random sample (T/T = 92.6%, T/C = 92.0%, C/T = 91.7%, C/C = 89.8%). Regression-line analyses of zones of inhibition versus MIC values for the four combinations showed coefficients of correlation to be −0.81, −0.76, −0.77, and −0.75, respectively. With the sample selected as being resistant to C, T was better than C for predicting T susceptibility (
P
< 0.05), and T was equivalent to C for predicting C susceptibility (T/T = 84.3%, T/C = 81.0%, C/T = 73.6%, C/C = 80.4%). Coefficients of correlation were −0.70, −0.74, −0.55, and −0.61, respectively. T and C disks were, therefore, equivalent for determining T and C susceptibilities, but the T disk was more reliable for determining T susceptibility in a population skewed with C-resistant strains.
In Vitro Response to Chloramphenicol, Tetracycline, Ampicillin, Gentamicin, and Beta-Lactamase Production by Halophilic Vibrios from Human and Environmental Sources
Authors: Joseph Sam W. , DeBell Robert M. , Brown Wendell P.
Published: June 2012

Isolates of
Vibrio parahaemolyticus
and
V. alginolyticus
from human and environmental sources were examined for antibiotic susceptibility by the methods of minimal inhibitory concentration (MIC) in broth and agar diffusion. These strains were found to be almost uniformly susceptible to chloramphenicol and tetracycline within attainable serum levels. The relationships of zone sizes to MICs for these two antimicrobial agents and ampicillin conformed essentially to those obtained by standard methods with gram-negative rods. Most strains were resistant to ampicillin and exhibited β-lactamase activity, which accounted for this resistance. Nine of 30
V. alginolyticus
strains from environmental sources were ampicillin resistant but did not produce measurable amounts of β-lactamase. Three strains exhibited multiresistance to high concentrations of chloramphenicol, tetracycline, and ampicillin, which suggests the presence of plasmids. Although the great majority of vibrios appeared to be susceptible to gentamicin by agar diffusion, susceptibility could not be measured by MIC because the added NaCl, required for growth by the halophilic vibrios, diminished gentamicin activity.
Comparative Activities of Selected Beta-Lactam Antibiotics Against
Haemophilus influenzae
Authors: Jorgensen James H. , Alexander Gary A.
Published: June 2012

The comparative activities of ampicillin, cefamandole, cefoxitin, cefaclor, and cefatrizine against both beta-lactamase-producing and non-beta-lactamase-producing isolates of
Haemophilus influenzae
were determined by using an agar dilution susceptibility test procedure. Ampicillin was the most active drug tested against non-beta-lactamase-producing isolates, whereas cefamandole was most active against beta-lactamase-producing strains.
In vitro assays of the efficacy of antimicrobial agents in controlling Chlamydia trachomatis propagation
Authors: Lee C K , Bowie W R , Alexander E R
Published: June 2012

The antimicrobial susceptibility of a low-laboratory-passage, slow-growing, genital Chlamydia trachomatis strain was studied by five different procedures with the use of McCoy cells pretreated with 5-iodo-2-deoxyuridine. The effects of antimicrobial agents when added to cultures on day 0 or day 2 after inoculation with C. trachomatis and the effects of washing and reincubating treated cultures in antimicrobial-free media were investigated. Tetracycline and erythromycin inhibited C. trachomatis growth at concentrations attainable in human serum, although their actions were reversible and significantly higher concentrations were needed to "cure" 48-h infected cultures. On a weight basis, spectinomycin was relatively ineffective in inhibiting C. trachomatis growth. The minimal inhibitory concentration of penicillin measured by our assay procedures was higher than that reported by other investigators. The five assay procedures used in this study were reproducible, and our results indicate that we can obtain more pertinent information about the efficacy of an antimicrobial agent in controlling C. trachomatis growth by using a combination of these assays than by simple minimal inhibitory concentration determinations, as had been previously described by other investigators. In addition, we failed to demonstrate changes in tetracycline susceptibility of C. trachomatis isolates from two patients who had received tetracycline therapy.
5-Propyl-2'-deoxyuridine: a specific anti-herpes agent
Authors: De Clercq E , Descamps J , Shugar D
Published: June 2012

In both primary rabbit kidney cells and human skin fibroblasts, 5-propyl-2'-deoxyuridine proved inhibitory to herpes simplex virus at a concentration as low as 1 micrograms/ml, whereas concentrations higher than 200 micrograms/ml were required to inhibit vaccinia virus replication or normal cell metabolism.
New In Vitro Model to Study the Effect of Antibiotic Concentration and Rate of Elimination on Antibacterial Activity
Authors: Grasso S. , Meinardi G. , De Carneri I. , Tamassia V.
Published: June 2012

A new apparatus is described which serves to investigate the in vitro antibacterial activity of antibiotics as a function of different concentration time curves. The apparatus can be adjusted to simulate the biexponential serum level curves observed in vivo after oral or intramuscular administration. Preliminary studies were carried out with a cephalosporin derivative, cefazolin, against
Escherichia coli
and
Klebsiella
sp. strains simulating initial concentrations of 5, 10, and 20 μg/ml that decreased exponentially with half-lives of 30, 60, and 120 min. Surviving cells were counted at 1-h intervals for 10 h. In all the situations tested there was an initial phase of rapid bactericidal activity followed by a phase of bacteriostatic activity, whose length depended on the drug elimination rate but was relatively independent of the initial concentrations. Bacterial regrowth occurred when the antibiotic concentration fell below the minimum inhibitory concentration of the drug against the strains tested. The antibacterial activity of cefazolin, cephacetrile, and cephradine against
E. coli
and
Klebsiella
strains was also investigated, in a medium containing 4% human albumin, simulating the serum level curves observed in humans after an intramuscular dose of 1 g. The results obtained suggest that, for cephalosporins, a longer half-life might be more useful than higher peak levels.
Cefaclor: In Vitro Spectrum of Activity and Beta-Lactamase Stability
Authors: Neu Harold C. , Fu Kwung P.
Published: June 2012

The in vitro activity of cefaclor against 556 clinical isolates of gram-positive and gram-negative bacteria was compared with that of other cephalosporins. Cefaclor had activity similar to that of cephalexin against gram-positive bacteria. It showed greater activity against
Haemophilus
strains than did cephalexin and inhibited β-lactamase-producing
Haemophilus
isolates. Cefaclor was more active than cephalexin or cephalothin against
Escherichia coli, Salmonella,
and
Shigella
isolates but did not act against
Serratia, Acinetobacter,
indole-positive
Proteus,
or
Bacteroides
isolates. Cefaclor was resistant to type III (TEM) β-lactamases but was destroyed by type I β-lactamases and, to a lesser degree, by type IV and type V β-lactamases.
Cetocycline, Tetracycline Analog: In Vitro Studies of Antimicrobial Activity, Serum Binding, Lipid Solubility, and Uptake by Bacteria
Authors: Proctor Richard , Craig William , Kunin Calvin
Published: June 2012

Cetocycline (formerly chelocardin or cetotetrine) is structurally related to the tetracyclines. It was found to be more active than tetracycline against many clinical isolates of aerobic gram-negative bacilli, but is less active against staphylococci, and has no activity against
Pseudomonas
. It is bactericidal against susceptible enteric gram-negative bacteria at concentrations two to four times higher than the minimal inhibiting concentrations. The drug is highly lipid soluble; more than 80% is bound to serum, and it is more avidly taken up by susceptible bacteria than tetracycline. A direct correlation between drug uptake and susceptibility of bacteria was not noted, except with a strain of
Proteus vulgaris
.
Contribution of a TEM-1-Like Beta-Lactamase to Penicillin Resistance in
Neisseria gonorrhoeae
Authors: Bergström Sven , Norlander Lena , Norqvist Anders , Normark Staffan
Published: June 2012

Two β-lactamase-producing strains of
Neisseria gonorrhoeae
were studied. The substrate profile, molecular weight, and isoelectric point of their β-lactamases were similar to those of the TEM-1 enzyme produced by many gram-negative bacilli. The gonococcal β-lactamase was cell bound during exponential growth and was most likely located in the periplasm. Penicillin hydrolysis was efficient in intact cells, suggesting that the cell-bound β-lactamase was freely accessible to benzylpenicillin. Both β-lactamase-producing strains of
N. gonorrhoeae
contained an additional multicopy plasmid with a mass of 3.3 megadaltons (Mdal). A spontaneous penicillin-susceptible revertant lacked both β-lactamase activity and the 3.3-Mdal plasmid, providing evidence for plasmid-mediated penicillin resistance. During a shift from GC medium to rich MOPS medium, growth of the penicillin-susceptible revertant in contrast to that of the plasmid-carrying strain was markedly impaired, suggesting a physiological effect due to the presence of the 3.3-Mdal plasmid.
Antimicrobial Susceptibility Patterns of
Streptococcus pneumoniae
Authors: Cooksey Robert C. , Facklam Richard R. , Thornsberry Clyde
Published: June 2012

Fifty clinical isolates of
Streptococcus pneumoniae
received by the Streptococcus Laboratory of the Center for Disease Control from August 1976 through March 1977 and 50 pneumococcal strains retrieved from 13- to 16-year storage (originally isolated October 1961 through December 1964) were tested for susceptibility to 10 antimicrobial agents by disk-agar diffusion and agar dilution tests. No appreciable differences in susceptibility patterns were apparent between the two groups, and, except for one isolate, all were highly susceptible to every drug tested except gentamicin. This single isolate required higher drug concentrations to inhibit macroscopic growth and had corresponding decrements in zones of disk inhibition with penicillin, ampicillin, and cephalothin. An additional 43 pneumococci recently received from various areas of the United States and Canada were screened by a disk agar diffusion method for penicillin resistance. Four of these isolates had penicillin zone diameters <30 mm, and subsequent agar dilution test results showed that the penicillin minimum inhibitory concentrations were elevated with these organisms. Antimicrobial susceptibility patterns of pneumococci to antimicrobials other than penicillin and its analogs have not changed substantially in over a decade. However, due to the emergence of strains with decreased susceptibility to penicillin, the screening test for penicillin resistance in pneumococci, especially in isolates from spinal fluid and blood, could be clinically useful as an aid in selecting optimal therapy.
Mode of Action of Quindoxin and Substituted Quinoxaline-di-
N
-Oxides on
Escherichia coli
Authors: Suter W. , Rosselet A. , Knüsel F.
Published: June 2012

The effect of quindoxin on the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid, and protein in
Escherichia coli
KL 399 was examined under aerobic and anaerobic conditions. In the absence of oxygen the synthesis of DNA was completely inhibited by 10 ppm of quindoxin, whereas the syntheses of ribonucleic acid and protein were not affected. Quinoxalin-di-
N
-oxides (QdNO) induce degradation of DNA in both proliferating and non-proliferating cells.
polA, recA, recB, recC, exrA
, and
uvrA
mutants were more susceptible than the corresponding repair-proficient strains. All strains were more resistant in the presence of oxygen. Quindoxin was reduced to quinoxalin-
N
-oxide by intact
E. coli
cells or by a cell-free
E. coli
extract. Electron spin resonance measurements demonstrated the generation of free radicals during the reduction of quindoxin. Oxygen or deficiency of energy sources impaired the antibiotic activity and the reduction of QdNO. The QdNO reductase activity was demonstrated to be lower in QdNO-resistant mutants than in the susceptible parent strain. Based on these results it is concluded that an intermediate of reduction, probably a free radical, is responsible for the lethal effect of quindoxin. With three independent techniques no evidence has been found for binding of quindoxin to DNA.
SK&F 75073, New Parenteral Broad-Spectrum Cephalosporin with High and Prolonged Serum Levels
Authors: Actor Paul , Uri Joseph V. , Zajac Ihor , Guarini Joseph R. , Phillips Lillian , Pitkin Donald H. , Berges David A. , Dunn George L. , Hoover John R. E. , Weisbach Jerry A.
Published: June 2012

SK&F 75073, a new parenteral cephalosporin, was found to have broad in vitro and in vivo antibacterial activity including isolates usually resistant to cephalothin and cefazolin. This activity included indole-positive
Proteus
and
Enterobacter
species and some
Serratia
isolates.
Proteus mirabilis
strains were particularly susceptible, as were
Haemophilus influenzae
and
Neisseria
species. The activity of SK&F 75073 against gram-positive bacteria was poorer than that of the control cephalosporins. This cephalosporin is highly bound to serum proteins, and a loss in in vitro activity was observed in the presence of serum. Parenteral administration of SK&F 75073 to experimental animals (mice, dogs, squirrel monkeys) resulted in high and prolonged serum levels when compared with cefazolin and other injectable cephalosporins. This favorable serum profile was reflected in the excellent protection observed in mice infected with pathogenic bacteria.