bluuebunny/crossref_metadata_2025 huggingface dataset:
Relation of Cell Wall Lipid Content of
Serratia marcescens
to Resistance to Antimicrobial Agents
Authors: Winshell Elaine B. , Neu Harold C.
Published: June 2012

Serratia marcescens
strains were divided into three groups on the basis of antimicrobial sensitivity and pigment production. Group I, nonpigmented, was resistant to most antibiotics. Group II, nonpigmented, was susceptible to many antimicrobial agents, as was group III which was pigmented. Representative organisms of each group were examined for all lipid content. There were no significant differences in total lipid, phospholipid, or fatty acid esters among the three groups. Differences in susceptibility to antibiotics in
Serratia
do not seem to be explained on the basis of wall lipid content.
Characteristics and Expression of Tetracycline Resistance in Gram-Negative Bacteria Carrying the
Pseudomonas
R Factor RP1
Authors: Shipley Patricia L. , Olsen Ronald H.
Published: June 2012

The
Pseudomonas
R factor RP1 determines an inducible tetracycline resistance similar to that described for
Escherichia coli
R factors. The level of RP1-determined resistance measured by minimal inhibitory concentration testing is dependent on the host bacteria and corresponds to the magnitude of decrease in tetracycline accumulation by RP1-containing organisms. The tetracycline resistance mechanism is inactivated at low temperatures. The effect of metabolic inhibitors on tetracycline accumulation by susceptible organisms under various conditions indicates a possible nonspecific effect of cellular energy metabolism on tetracycline uptake.
Effect of the Inhibition of Protein Synthesis on the
Escherichia coli
Cell Envelope
Authors: Klainer A. S. , Russell R. R. B.
Published: June 2012

The consequences for cell envelope integrity of
Escherichia coli
K-12 of the inhibition of protein synthesis by a variety of means have been examined. Protein synthesis was blocked by the antibiotics chloramphenicol and streptomycin, by amino acid starvation of an amino acid auxotroph, and by inactivation of temperature-sensitive aminoacyl transfer ribonucleic acid synthetase and ribosomal mutations. Closely similar morphological and physiological effects were found irrespective of the means by which protein synthesis was blocked. Scanning electron microscopy revealed a spectrum of changes after protein inhibition, with granular material derived from cells and spheroplasts commonly seen. Streptomycin caused additional changes manifested in a collapsed appearance of treated cells. Measurements of the release of lipopolysaccharide from the cell surface, alterations in outer membrane penetrability, and lysis of lysozyme-ethylenediaminetetraacetic acid-treated cultures also showed that the various inhibitory treatments all had similar effects on cell envelope properties. The close correspondence between the effects seen with antibiotic-treated cultures and those in which protein synthesis inhibition was achieved by use of mutants indicates that the effects of chloramphenicol and streptomycin on the cell envelope are indirect consequences of ribosomal block, rather than due to multiple sites of action of the antibiotics.
Speed of Bactericidal Action of Penicillin G, Ampicillin, and Carbenicillin on
Bacteroides fragilis
Authors: Schoutens E. , Yourassowsky E.
Published: June 2012

In order to determine the therapeutic value of penicillins in the management of anaerobic infections caused by
Bacteroides fragilis
, the antibacterial activity of penicillin G, ampicillin, and carbenicillin against 10 strains of
B. fragilis
subsp.
fragilis
, isolated from clinical material, was studied. This was undertaken by using a triple-layer technique, enzymatic inactivation of the antibiotics, and an automatic colony counter, which allowed a quantitative and a qualitative approach to the problem. Results indicated in vitro bactericidal activity with 40 μg of penicillin G, ampicillin, and carbenicillin per ml against all strains tested. However, carbenicillin had the most rapid activity.
Synthesis of Deactoxycephalosporin C by a Mutant of
Cephalosporium acremonium
Authors: Queener S. W. , Capone J. J. , Radue A. B. , Nagarajan R.
Published: June 2012

A number of
Cephalosporium acremonium
mutants blocked in the synthesis of cephalosporin C were investigated for accumulation of other β-lactam compounds. The non-cephalosporin C producers were isolated after exposing the superior cephalosporin C-producing strain M8650-4 to ultraviolet light (268 nm). One of the blocked mutants, MH63, accumulated deacetylcephalosporin C (0.4 mg/ml), deacetoxycephalosporin C (1.5 mg/ml), and penicillin N (2.7 mg/ml). In contrast, the parent of MH63 produced high levels of cephalosporin C as well as deacetylcephalosporin C (2.2 mg/ml) and penicillin N (1.0 mg/ml), but only traces of deacetoxycephalosporin C (about 0.1 mg/ml). Deacetoxycephalosporin C was isolated from the mutant strain and identified by ultraviolet light, nuclear magnetic resonance, bioactivity spectrum, and co-migration with authentic standard in three chromatography systems.
Effects of Rate of Infusion and Probenecid on Serum Levels, Renal Excretion, and Tolerance of Intravenous Doses of Cefoxitin in Humans: Comparison with Cephalothin
Authors: Goodwin C. Stewart , Raftery E. B. , Goldberg A. D. , Skeggs H. , Till A. E. , Martin C. M.
Published: June 2012

Using a randomized crossover design, 1-g intravenous doses of cephalothin and cefoxitin, a cephalosporinase-resistant cephamycin, were infused into 12 normal adult males over periods of 120, 30, and 3 min, the last with and without prior intravenous infusions of probenecid (1 g). Mean peak serum concentrations of antibiotic activity after cephalothin infusions were 23, 56, 103, and 102 μg/ml, respectively, and after cefoxitin infusions they were 27, 74, 115, and 125 μg/ml, respectively. Probenecid treatment prolonged the terminal serum half-life of cephalothin-like activity from 0.52 to 1.0 h, and of cefoxitin from 0.68 to 1.4 h. In contrast to cephalothin, which was found to be metabolized about 25% to the less active desacetyl form, cefoxitin was metabolized less than 2% to the virtually inactive descarbamyl form, as judged from urinary recoveries. Neither antibiotic displayed detectable organ toxicity. Of 300 recent clinical isolates of gram-negative bacilli other than
Pseudomonas
spp., 83% were susceptible to cephalothin but 95% were susceptible to cefoxitin. Organisms resistant to cephalothin but susceptible to cefoxitin included strains of
Escherichia coli, Proteus vulgaris, Klebsiella
spp.,
Serratia marcescens, Enterobacter
spp., and
Bacteroides
spp.
Evaluation of Aquarium Antibiotic Formulations
Authors: Trust T. J. , Chipman Diane C.
Published: June 2012

The antibacterial activity of eight products marketed for the therapy and prophylaxis of diseases of ornamental fishes was tested. The products contained erythromycin, neomycin, a nitrofuran, penicillin, sulfa compounds, streptomycin, or tetracycline. When used at the concentration recommended by the manufacturer, the products failed to inhibit the growth of bacterial species known to be potential pathogens of ornamental fishes and failed to reduce significantly the bacterial numbers in water containing fish. Concentrations of the products that were bacteriostatic were markedly higher than the in-use concentration recommended by the manufacturer. The danger presented by the unrestricted availability of antibiotic compounds frequently used in the treatment of human and animal disease is discussed.
Cell Culture Studies on the Antiviral Activity of Ether Derivatives of 5-Hydroxymethyldeoxyuridine
Authors: Meldrum J. B. , Gupta V. S. , Saunders J. R.
Published: June 2012

The antiviral activity of several ether derivatives of 5-hydroxymethyldeoxyuridine against the herpesvirus of infectious bovine rhinotracheitis was determined in monolayer cultures of secondary bovine fetal kidney cells. 5-Methoxy-methyldeoxyuridine (OCH
3
UdR) was found to be markedly inhibitory against this virus. Pretreatment of the cells with OCH
3
UdR, simultaneous addition of OCH
3
UdR with virus to the cells, and postinfection treatment with OCH
3
UdR were found to be effective in inhibiting virus-induced cytopathogenic effect. Against this virus, OCH
3
UdR was found to be as potent as 5-iododeoxyuridine and cytosine arabinoside. The α-anomer of OCH
3
UdR did not show antiviral activity. Preliminarly toxicity studies indicate that OCH
3
UdR has a very low acute toxicity.
Ampicillin Resistance of
Shigella sonnei
Authors: Smith J. T. , Bremner D. A. , Datta Naomi
Published: June 2012

The ampicillin resistance of clinical isolates of
Shigella sonnei
is due to β-lactamase production. Two kinds of resistance are found: low level, nontransmissible; and high level, tranmissible. The nontransmissible type of resistance results from a chromosomal mutation which increases the production of a β-lactamase that hydrolyses cephalosporins relatively rapidly and gives cephalothin resistance. The transmissible type of resistance is due to an R factor mediating the synthesis of a different β-lactamase that does not significantly hydrolyze cephalosporins or confer cephalothin resistance. One clinical isolate is shown to possess simultaneously both these mechanisms of ampicillin resistance.
Comparison of the In Vitro Activity of BL-P1654 with Gentamicin and Carbenicillin Against
Pseudomonas aeruginosa
Authors: Watanakunakorn Chatrchai , Bannister Thomas
Published: June 2012

The in vitro activity of 6-[
d
-α-(3 guanylureido)-phenylacetamido]-penicillanic acid (BL-P1654) was evaluated against 117 clinical isolates of
Pseudomonas aeruginosa
, many of which were known to be resistant to both gentamicin and carbenicillin. BL-P1654 was two to eight times more active than carbenicillin against
P. aeruginosa
. However, all 28 highly carbenicillin-resistant isolates (minimal inhibitory concentration [MIC] > 500 μg/ml) were also highly resistant to BL-P1654. When an MIC of 32 μg/ml or less and a zone of inhibition of 12 mm or more by a 10-μg disk were used as criteria indicating susceptibility to BL-P1654, the false-resistance rate by the disk test was 10.6% and the false-susceptibility rate was 4.2%. The combination of BL-P1654 and gentamicin was synergistic against 45 of 70 isolates of
P. aeruginosa
tested, but synergism was demonstrated against only 4 of 24 highly gentamicin-resistant (MIC > 63 μg/ml), 1 of 12 highly BL-P1654-resistant (MIC > 250 μg/ml) isolates, and none of nine isolates highly resistant to both of these antibiotics.
Isolation and Characterization of a Kanamycin Resistance Plasmid from
Staphylococcus aureus
Authors: Stiffler Paul W. , Sweeney H. M. , Schneider M. , Cohen Sidney
Published: June 2012

A circular covalently closed duplex deoxyribonucleic acid plasmid carrying genes for resistance to kanamycin/neomycin has been identified in
Staphylococcus aureus
E419. The plasmid has a molecular size of 9.2 × 10
6
daltons and can be transduced into or can transform competent susceptible strains of
S. aureus
to kanamycin/neomycin resistance.
Detection of R Factors in Naturally Occurring
Vibrio anguillarum
Strains
Authors: Aoki Takashi , Egusa Syuzo , Arai Toshihiko
Published: June 2012

R factors were detected in
Vibrio anguillarum
strains from vibrio-diseased freshwater fish, ayu (
Plecoglossus altivelis
), in Japan. It was found that 65 out of the 68 random isolates from epidemics of vibrio disease in 1973 carried transferable drug resistance factors. The most common type determined resistance to sulfonamides, streptomycin, chloramphenicol, and tetracycline and belong to the
fi
−
type. The high incidence of R factors in
Vibrio anguillarum
from cultured fish is assumed to be due to selective pressure exerted by chemotherapeutic agents used in fish culturing.
Evaluation of the Efficacy of Minocycline Therapy for Staphylococcal Soft-Tissue Infection
Authors: Phair John P. , Hartman Rae E. , Carleton Judith
Published: June 2012

Ten patients with soft-tissue infections due to
Staphylococcus aureus
were treated with minocycline, a semisynthetic tetracycline with potent in vitro antistaphylococcal effects. Serum concentrations averaged three to five times the concentration of minocycline required to inhibit growth of
S. aureus
in vitro. Clearing of the infecting organism was slow (less than 50% of lesions were sterile on day 10 of therapy), but clinical improvement was noted in 8 of 10 patients.
Immunogical Study of Anti-Beta-Lactamase Antibodies by Acidimetric Methods
Authors: Le Goffic François , Andrillon-Spiegel Jane , Letarte Robert
Published: June 2012

A beta-lactamase was extracted from an
Escherichia coli
K-12 strain carrying the R-TEM plasmid and has been purified by affinity chromatography. Antisera to this enzyme were prepared in the rabbit, and the enzyme-antibody neutralization reaction has been evaluated with acidimetric methods (pH stat or pH meter). Under defined experimental conditions, it is now possible to clearly illustrate the enzyme-antibody reaction by means of accurate, rapid, and simple-to-perform methods. These methods are in accord with the specificity of the two reactive partners and allow the detection of the enzyme in a crude bacterial extract which would eventually contain more than one beta-lactamase.
Generation of Formaldehyde from Methenamine: Effect of pH and Concentration, and Antibacterial Effect
Authors: Musher Daniel M. , Griffith Donald P.
Published: June 2012

Using an in vitro system that simulates the dynamics of the urinary tract, we have shown that concentrations of formaldehyde ≥ 25 μg/ml can be achieved in urine containing ≥ 0.6 mg of methenamine per ml at pH ≤ 5.7 or ≥ 1 mg/ml at pH ≤ 5.85. Exposure to this concentration of formaldehyde for 2 h produced a measurable antibacterial effect. These studies suggest that an effective bacteriostatic level of formaldehyde is likely to be achieved with currently used dosages of methenamine when the urine pH is less than 5.7 to 5.85.
Human Pharmacokinetics of BL-P1654 Compared with Ampicillin
Authors: Clarke John T. , Libke Robert D. , Ralph Edward D. , Luthy Ruedi P. , Kirby William M. M.
Published: June 2012

BL-P1654 is a new ureido-penicillin which has significant activity against both pseudomonas and klebsiella. Its pharmacokinetics were evaluated in five studies in four healthy adult male volunteers after 1-g doses given as: 5- and 30-min intravenous infusions, a 30-min infusion 1 h after the oral administration of 1 g of probenecid, and an intramuscular injection. For comparison, volunteers also received a 30-min infusion of 1 g of ampicillin. Serum levels of the antibiotic were found to fit a two-compartment open model using a Burroughs-5500 computer. After a 30-min infusion, peak serum levels of BL-P1654 (72.8 μg/ml [standard deviation] ± 5.9) were 50% greater than those of ampicillin (53.6 ± 8.9). Six hours later, the relative difference was even greater (4.58 ± 0.25 versus 0.35 ± 0.09). At 75 min after the 1-g intramuscular injection of BL-P1654, peak serum levels averaged 28.4 ± 10.3 μg/ml. The half-life of BL-P1654 (2.04 h) was significantly longer than for ampicillin (1.15 h), and the renal clearances of BL-P1654 and ampicillin were 79 versus 244 ml/min per 1.73 m
2
, respectively. Probenecid produced no significant change in blood levels, volume of distribution, half-life, or renal clearance, indicating that there is no net tubular secretion of this antibiotic.
In Vitro Inhibition of
Coccidioides Immitis
Strains with Amphotericin B Plus Rifampin
Authors: Rifkind David , Crowder Ellen D. , Hyland Robert N.
Published: June 2012

Rifampin was shown in vitro to decrease the amphotericin B minimal inhibitory concentrations of all of 10 strains of
Coccidioides immitis
tested. These decreases ranged from two- to fourfold and occurred with rifampin concentrations of 10 to 40 μg/ml. Rifampin alone was without effect.
Properties of R Factors from
Bordetella bronchiseptica
Authors: Terakado Nobuyuki , Mitsuhashi Susumu
Published: June 2012

Genetic properties and host ranges of R factors derived from
Bordetella bronchiseptica
of pig origin were examined. All of 61 R factors tested could confer resistance to streptomycin, sulfonamide, and aminobenzyl penicillin on their host bacteria. All of them were identified as
fi
−
(no fertility inhibition) type and were found to exhibit no restriction of phages λ, φ80, P1, P2, T1, T3, T6, T7, W31, and BF-23. They could confer macarbomysin susceptibility on their host cells when infected. An Rte16, a representative R factor, was incompatible with both RP4 and R40a, which are classified as compatibility groups P and C, respectively. An Rte16 was conjugally transmissible to
B. bronchiseptica, Escherichia coli, Citrobacter freundii, Salmonella typhimurium
, and
Yersinia enterocolitica
, but not to
Shigella flexneri, S. sonnei, Proteus mirabilis, P. vulgaris, P. rettgeri, Klebsiella pneumoniae
, and
Pseudomonas aeruginosa
.
Effect of Isoniazid on the Protoplasmic Viscosity in
Mycobacterium tuberculosis
Authors: Takayama Kuni , Keith Alec D. , Snipes Wallace
Published: June 2012

The effect of isoniazid on the protoplasmic viscosity in the H37Ra strain of
Mycobacterium tuberculosis
was determined by using electron spin resonance spectroscopy and a small spin label tempone (2,2,6,6-tetramethylpiperidone-
N
-oxyl radical). Isoniazid (0.5 μg/ml) caused the internal cellular viscosity to increase gradually over the first 15 h of exposure from a rotational correlation time value (
T
c
) of 2.4 × 10
−10
to 3.4 × 10
10
s and then decrease linearly to the control level after 27 h. These results could be interpreted to mean that isoniazid allows a continued and normal synthesis of the protoplasmic components while the rate of increase in the cell volume is reduced. A degradative process may begin after the initial 15-h exposure time, which would cause the reduction in the internal viscosity.
Acetylation of Amikacin, a New Semisynthetic Antibiotic, by
Pseudomonas aeruginosa
Carrying an R Factor
Authors: Kawabe Haruhide , Naito Takayuki , Mitsuhashi Susumu
Published: June 2012

A clinical isolate
Pseudomonas aeruginosa
GN315 resistant to amikacin (AK), a new semisynthetic antibiotic, inactivated AK by acetylation. The acetylating enzyme was purified approximately 146-fold from a crude extract of GN315 by affinity chromatography. Fractionated samples obtained by affinity chromatography showed almost the same inactivation curves toward 3′,4′-dideoxykanamycin B (DKB) and AK. Partially purified AK-acetylating enzyme inactivated DKB and kanamycin A but could not inactivate gentamicin C
1
. The optimal pH for their inactivation was 6.0 to 7.0, and the pH curves for the inactivation of both drugs were almost the same. These facts indicate that AK and DKB are inactivated by the same aminoglycoside-acetylating enzyme. Through elemental analysis, the inactivated AK was found to be a monoacetylated product of AK. A sample of inactivated AK was purified and compared with a synthetic 6′-
N
-acetyl AK by thin-layer chromatography, and the results indicated that AK was inactivated by acetylation of the 6′-NH
2
group. The ultraviolet, infrared, and nuclear magnetic resonance spectra of the inactivated AK showed that AK was inactivated by the enzyme through acetylation of the amino group of 6′-amino-6′-deoxy-
d
-glucose moiety of AK. This enzyme, mediated by R factor, is capable of conferring resistance to AK, DKB, kanamycin, gentamicin, and sulfanilamide.
Comparative Effect of Tetracycline and Doxycycline on the Occurrence of Resistant
Escherichia coli
in the Fecal Flora
Authors: Bartlett John G. , Bustetter Larry A. , Gorbach Sherwood L. , Onderdonk Andrew B.
Published: June 2012

Antibiotic-induced changes in the fecal microflora after oral administration of tetracycline hydrochloride and doxycycline for 8 to 10 days were compared. A significant difference was noted in the concentrations of
Escherichia coli
resistant to tetracyclines. With tetracycline hydrochloride, there was a mean increase of approximately 10
4
resistant strains per g compared to only 10
1
/g for doxycycline. This difference is ascribed to reduced intestinal concentrations of bioactive drug with recommended oral dosage for doxycycline.
Parenteral Clindamycin Phosphate: Pharmacology with Normal and Abnormal Liver Function and Effect on Nasal Staphylococci
Authors: Williams D. N. , Crossley Kent , Hoffman Carol , Sabath L. D.
Published: June 2012

Parenteral clindamycin was evaluated in 41 patients with a variety of infections. The four major findings were as follows. (i) Five hours after the intravenous administration of 600 mg of clindamycin, the mean serum concentration in patients with “moderate to severe” hepatic dysfunction was 24.3 μg/ml, and in those with normal liver function it was 8.3 μg/ml (
P
< 0.02). This suggests that the dose of clindamycin might be modified in patients with liver disease. (ii) There was a positive association between the 5-h serum clindamycin level and the degree of elevation of the serum glutamic oxaloacetic transaminase. (iii) No significant side effects were observed. Of 24 patients with preexisting hepatic dysfunction, 5 showed deterioration and 5 showed improvement of liver function during therapy. (iv) Whereas all pre-treatment isolates of
Staphylococcus epidermidis
from the anterior nares were susceptible to clindamycin, 6 of 9 post-treatment isolates were resistant, most probably due to selection of resistant organisms.
Susceptibility of Various Serogroups of Streptococci to Clindamycin and Lincomycin
Authors: Karchmer Adolf W. , Moellering Robert C. , Watson Barbara K.
Published: June 2012

The minimal inhibitory concentration of lincomycin and clindamycin for a large number of strains from multiple serogroups of streptococci was determined. The median minimal inhibitory concentration for streptococci from groups A, B, C, F, G, H, L, and M and nongroupable organisms ranged from 0.02 to 0.39 μg of lincomycin per ml and from ≤0.01 to 0.09 μg of clindamycin per ml. Among the group D strains,
Streptococcus faecium
and
Streptococcus faecalis
were resistant to lincomycin and clindamycin, whereas
Streptococcus bovis
and four American strains of
Streptococcus durans
resembled nongroup D isolates in their susceptibility to these agents. Occasional strains of nongroup D streptococci were highly resistant to lincomycin and clindamycin.
Activity of Three Aminoglycosides and Two Penicillins Against Four Species of Gram-Negative Bacilli
Authors: Weinstein Ralph J. , Young Lowell S. , Hewitt William L.
Published: June 2012

Three aminoglycoside antibiotics and two penicillins were compared for their in vitro activity against 60 isolates of
Serratia, Pseudomonas, Proteus mirabilis
, and indole-positive
Proteus
sp. Testing was done by the agar dilution method using Mueller-Hinton broth solidified with 1.5% agar. The activity of amikacin, aminodeoxybutirosin, and gentamicin against
Proteus
and
Pseudomonas
, as related to their peak blood levels, showed no significant differences. Amikacin was the most active against
Serratia marcescens
. Results using Mueller-Hinton media in broth dilution tests correlated with the agar dilution method except for
Pseudomonas aeruginosa
. The minimal inhibitory concentration for aminoglycosides in agar was considerably greater than the minimal inhibitory concentration in Mueller-Hinton broth, and the disparity was related to the higher divalent cation concentration of agar. BL-P1654 and carbenicillin were similar except that carbenicillin was much more active against indole-positive
Proteus
sp. Additionally, the ratio of bactericidal to bacteriostatic concentrations of BL-P1654 was considerably greater than for carbenicillin.
Activity of Cefazolin Against Dense Populations of Enterobacteria
Authors: Greenwood D. , Chan-Teoh C. H. , O'Grady F.
Published: June 2012

The in vitro activity of cefazolin was assessed by continuous turbidimetric monitoring of cultures of gram-negative bacilli and the results were compared with those previously obtained with other beta-lactam agents using the same strains and methods. Cefazolin was found to induce rapid lysis of ampicillin-susceptible and -resistant strains of
Escherichia coli
at a lower concentration than any other beta-lactam agent tested; its stability to beta-lactamase, as judged by regrowth studies, was generally considerably greater than that of other antibiotics of this group. Tested against 103 ampicillin-resistant enterobacteria, cefazolin was found to be more active than cephalothin against
E. coli
, but no systematic increase in susceptibility to cefazolin was seen with other species. A study of cefazolin in an in vitro model which simulates the hydrokinetic features of the urinary bladder showed it to be as active as ampicillin against ampicillin-susceptible
E. coli
and as active as cephalothin against ampicillin-resistant
E. coli
.
Differences in Susceptibility of
Enterobacteriaceae
and Penicillin-Resistant
Staphylococcus aureus
to Tetracycline and Minocycline
Authors: Candanoza Carmen , Ellner Paul D.
Published: June 2012

Two hundred strains of penicillin-resistant
Staphylococcus aureus
and 311 isolates of
Enterobacteriaceae
were compared for their susceptibility to tetracycline and minocycline. Thirteen and one-half percent of the staphylococcal isolates were resistant to tetracycline but susceptible to minocycline. Similarly, 24% of the enterobacterial isolates were found to be tetracycline resistant but susceptible to minocycline. Of a total of 511 recent clinical isolates, 14.5% were susceptible to minocycline but were tetracycline resistant.
Verdamicin, a New Broad Spectrum Aminoglycoside Antibiotic
Authors: Weinstein M. J. , Wagman G. H. , Marquez J. A. , Testa R. T. , Waitz J. A.
Published: June 2012

Verdamicin is a new aminoglycoside antibiotic isolated from fermentation broths of a species of the genus
Micromonospora, M. grisea
. It has been differentiated from other known related antibiotics by a variety of chemical and biological methods. Its in vitro and in vivo spectrum of activity appears to be similar to those of gentamicin and sisomicin.
Potentiation of the Toxicity of Mithramycin by Bacterial Lipopolysaccharide
Authors: Bradley S. G. , Adams A. C. , Smith M. C.
Published: June 2012

The lethality for BALB/c mice of 1,3-bis(2-chloroethyl)-1-nitrosourea, cytosine arabinoside, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, hydroxyurea, mithramycin, a polymyxin-like antibiotic (SQ 21,286), polyadenylic polyuridylic acid, procarbazine, 5-[3,3-bis(2-chloroethyl)-1-triazeno]-imidazole-4-carboxamide (TIC-mustard) or uracil arabinoside administered in combination with
Escherichia coli
lipopolysaccharide (LPS) was measured. Simultaneously administered mithramycin and LPS or TIC-mustard administered 24 h after LPS synergistically killed mice. Concanavalin A potentiated the lethality of TIC-mustard but not of eight other drugs tested. Pretreatment of mice with LPS or lipid A complexed to concanavalin A rendered mice resistant to the lethal action of LPS alone or combinations of LPS and mithramycin. Mithramycin-treated mice were killed by minute amounts of LPS. Mice sensitized to LPS by mithramycin were used to detect endotoxic activity in biological materials, such as commercially available enzymes, and in a complex of lipid A with concanavalin A.
Gentamicin and Gentamicin C
1
in the Treatment of Complicated Urinary Tract Infections: Comparative Study of Efficacy, Tolerance, and Pharmacokinetics
Authors: Mosegaard Aage , Welling Peter G. , Madsen Paul O.
Published: June 2012

The clinical efficacy, patient tolerance, and pharmacokinetics of gentamicin and the single component gentamicin C
1
were studied after single and multiple doses in elderly male patients. Patient tolerance was extremely good at the dose levels used. There was some evidence of renal function impairment due to repeated intramuscular doses of gentamicin, but not gentamicin C
1
. The antibiotics were equally effective against the organisms present in the urine of these patients. The pharmacokinetics of the two antibiotic forms were similar, although gentamicin C
1
appeared to have a larger distribution space.
BL-P1654: a Bacteriostatic Penicillin?
Authors: Sanders Christine C. , Sanders W. Eugene
Published: June 2012

In tube dilution studies, large discrepancies between inhibitory and bactericidal concentrations of BL-P1654 against
Pseudomonas
were observed. To explain these discrepancies which were not observed with carbenicillin, the kinetics of bacterial killing by these two penicillins were evaluated and compared. The kinetics of bacterial killing by both antimicrobial agents were characteristic of a penicillin, with killing initiating simultaneously with growth. Kill curves revealed the presence of a small number of cells resistant to BL-P1654 which were not detectable macroscopically. Studies on microbial resistance also showed the presence of a small but consistent number of cells resistant to BL-P1654 over a broad range of concentrations above its minimal inhibitory concentration. This pattern of resistance was not observed with carbenicillin. Thus, the discrepancies between inhibitory and bactericidal concentrations of BL-P1654 were not due to any unusual bacteriostatic activity but rather due to a small number of resistant cells whose presence could be detected only by sensitive subculturing techniques.
In Vivo Efficacy of 81.723 hfu, a New Pleuromutilin Derivative Against Experimentally Induced Airsacculitis in Chicks and Turkey Poults
Authors: Laber G. , Schütze E.
Published: June 2012

The efficacy of the pleuromutilin derivative 81.723 hfu was tested in chicks and turkey poults by experimentally infecting them with
Mycoplasma gallisepticum
. The data were treated to obtain the mean effective doses, and these were compared to those obtained with tylosin tartrate. The compounds were administered either by ingluvial catheter or via the drinking water. Therapy was started on the day of inoculation or 7 days thereafter, respectively. The experiments showed that the compound 81.723 hfu was significantly more active in chickens than tylosin tartrate by both methods of administration of drinking water. In turkey poults the pleuromutilin derivative and tylosin tartrate had comparable activity.
Inactivation of
Treponema pallidum
by Silver Sulfadiazine
Authors: Chang Te-Wen , Weinstein Louis
Published: June 2012

Silver sulfadiazine, an anti-infectious agent for the prevention and treatment of burn sepsis, has been found to possess antitreponemal activity against
Treponema pallidum
. At 28 C, complete inactivation of the organism was produced by exposure of the organism to a concentration of 50 μg of the drug per ml for 1 to 5 min, 12 to 25 μg/ml for 10 to 15 min, and 6.2 μg/ml for 30 min. At 37 C, the amounts of silver sulfadiazine required for inactivation were two- to fourfold less.
Effect of Tetracycline on Puromycin-Induced Polysome Degradation: Influence of Magnesium and Polyamines
Authors: Dionne Peter , Rosano Carmen L. , Hurwitz Charles
Published: June 2012

Puromycin-induced polysome degradation has been shown to require G factor, guanosine 5′-triphosphate, and the presence of a ribosome release factor (Hirashima and Kaji, 1972, 1973). Tetracycline, which does not inhibit formation of peptidyl-puromycin (Gottesman, 1967; Sarkar and Thach, 1968) nor the guanosine 5′-triphosphate hydrolysis mediated by elongation factor Tu (Ono et al., 1969), inhibits polysome degradation. The tetracycline inhibition requires Mg
2+
at concentrations above 8 mM, which are inhibitory to protein synthesis in vitro. At concentrations of Mg
2+
below 8 mM, polysome degradation is insensitive to tetracycline, but not to fusidic acid. Addition of spermidine, but not of other polyamines, enables the tetracycline inhibition to occur at concentrations of Mg
2+
as low as 2 mM. The inhibition by tetracycline and by fusidic acid suggests that ribosome movement may be essential for the function of ribosome release factor, or that these antibiotics may directly affect its action.
Antibacterial Activity of Cinoxacin In Vitro
Authors: Giamarellou Helen , Jackson George G.
Published: June 2012

Cinoxacin is a new synthetic compound similar chemically and in antimicrobial activity to oxolonic acid and nalidixic acid. It is most effective against
Escherichia coli
and
Proteus mirabilis
, but at concentrations expected in the urine it is inhibitory for all species of
Enterobacteriaceae
. Relative to nalidixic acid, cinoxacin has slightly greater inhibitory and bactericidal activity, less inoculum effect probably due to less heterogeneity in the susceptibility of bacterial cells, and less inhibition by high concentrations of serum protein. Both drugs are more active in an acid than an alkaline medium. Glucose can specifically antagonize the inhibitory effect against
P. mirabilis
. In urine the bactericidal rate and effect are decreased. Resistance to cinoxacin can be developed quickly by serial transfers in vitro. Some nonresistant organisms remained viable in bactericidal drug concentrations. The in vivo importance of the favorable features of cinoxacin must be determined by clinical trials.
Artificial Elimination of Drug Resistance from Group A Beta-Hemolytic Streptococci
Authors: Nakae Masataka , Inoue Matsuhisa , Mitsuhashi Susumu
Published: June 2012

Ten strains of beta-hemolytic streptococci were tested for elimination of resistance to macrolide antibiotics, tetracycline, and chloramphenicol. Six of the strains lost resistance after cultivation at 41 C or addition of acriflavine (0.2 μg/ml). These results suggest that determinants governing resistance to these antibiotics are located on extrachromosomal genetic elements (plasmids) that are widely distributed in streptococci.
Differential Potentiation by Nystatin of the Effect of Antibiotics on Yeast and Mammalian Cells
Authors: Aszalos Adorjan
Published: June 2012

The effect of the polyene antibiotic nystatin, used in combination with several other antibiotics, on the membranes of
Candida albicans
SC#8169 (yeast) cells and of Chinese hamster ovary and 3T3 (mammalian) cells was investigated. It was concluded from determinations of the viability of the yeast cells and from measurements of deoxyribonucleic acid synthesis by the mammalian cells that nystatin acts synergistically with several antibiotics on yeast cells, but not on CHO and 3T3 cells. This selective action of nystatin may prove useful in chemotherapy.
Renal and Biliary Disposition of Dapsone in the Dog
Authors: Biggs John T. , Uher Anne K. , Levy Louis , Gordon G. Ross , Peters John H.
Published: June 2012

Dapsone (4,4′-diaminodiphenylsulfone [DDS]) was administered intravenously to anesthetized dogs; urine was collected, heparinized venous blood was obtained, and bile was collected from some of the dogs. A constant infusion of inulin was maintained, and isosmotic or hypoosmotic fluids were administered. Dogs were studied under conditions of standardized, increased or decreased urine flow, and before and after plasmapheresis. Plasma, urine, and bile samples were analyzed for DDS and DDS conjugates; the degree of binding of DDS by plasma proteins was also determined. The renal clearances of inulin and DDS were calculated. No monoacetyldapsone (MADDS) was detected in the plasma, and only negligible quantities were found in the urine. Small quantities of DDS and DDS conjugates were detected in the bile in 4 h following the dose. Between 10 and 30% of the administered drug could be identified as DDS plus DDS conjugates in the urine in 8 h after the dose. Renal clearance of unbound DDS was proportional to the urine flow rate, and the clearance ratio of DDS to inulin approached the same maximal value as that for urea. Although the rate of urinary excretion of DDS conjugates was the same in the dog as in man, the rates of excretion of DDS and of DDS plus DDS conjugates were greater in the dog than in man, suggesting that the acetylation of DDS to MADDS by man but not by the dog and the greater degree of plasma protein binding of DDS and MADDS by man account for the longer half-time of disappearance of DDS in man compared to that in the dog.
Relationship Between Exoprotease Secretion and the Synthesis of Ribonucleic Acid and Protein in
Bacillus amyloliquefaciens
Authors: Coleman G. , Brown S.
Published: June 2012

Studies with washed bacteria suspended in fresh medium, in which bacterial densities were altered by a factor of four so as to cause accelerated entry of exponential bacteria into the postexponential phase and to re-establish growth in postexponential bacteria, have been performed. Under all the conditions examined rifampin, at a concentration of 0.5 μg/ml, inhibited [
14
C]uracil incorporation into total ribonucleic acid (RNA) by 90 to 95%. The percentage of inhibition of incorporation of
14
C-labeled amino acids into total protein achieved in parallel experiments was less, being not more than 80%. These results suggested that non-translatable RNA synthesis was inhibited more than messenger RNA (mRNA) by the antibiotic. It was found that on slowing the growth of exponential-phase bacteria exoprotease was formed at a high rate without a lag. It was further observed that when postexponential bacteria were induced to grow, by resuspending them at a lower density, exoprotease mRNA synthesis was switched off. The only synthesis of exoprotease which occurred in this case was accountable to pre-existing mRNA during its decay. Exoenzyme formation was found to be less susceptible to rifampin than total protein synthesis.
Effects of 5-Bromodeoxyuridine and 5-Iododeoxyuridine on a Latent Herpes Simplex Virus Infection
Authors: Varani J. , Kelleher J. J.
Published: June 2012

A latent herpes simplex virus infection was established in rabbit kidney cells. Treatment of the cells with 5-bromo-2-deoxyuridine after the latent infection was established had no effect on the rate of virus recovery but did extend the latent period before active virus growth resumed. In contrast to this, treatment of cells with 5-bromo-2-deoxyuridine or 5-iodo-2-deoxyuridine prior to infection with virus increased the subsequent rate of virus recovery.
Therapy of
Pseudomonas aeruginosa
Infections with Tobramycin
Authors: Blair Donald C. , Fekety F. Robert , Bruce Barbara , Silva Joseph , Archer Gordon
Published: June 2012

The efficacy of tobramycin in doses of 2.7 to 5.6 mg/kg per day in 29 courses of therapy in 25 hospitalized patients with serious
Pseudomonas aeruginosa
infections was studied. Eighty-three percent of the
P. aeruginosa
strains showed zones of inhibition of 16 mm or more around a 10-μg tobramycin disk in the Bauer-Kirby disk method. Tobramycin minimal inhibitory concentration ranged from <0.05 to 1.5 μg/ml (microtiter twofold dilution method); for gentamicin they ranged from 0.05 to 6.2 μg/ml; corresponding geometric means were 0.19 and 0.49 μg/ml. Therapy was given for a median of 10 days (mean 19, range 1 to 83). The clinically satisfactory response rate for the 29 courses of therapy was 52%: critically ill, 44%; seriously ill, 50%; moderately ill, 80%. The response rates for various sites of infection were bone and cartilage, 100%; urinary tract infection, 56%; wound, 50%; respiratory tract, 67%; septicemia, 40%; abscess, 0%; burns, 44%. No adverse reactions were seen. Serum concentration (μg/ml ± standard deviation) of tobramycin determined by an agar-well plate method, were 4.81 ± 2.17 (1 h); 3.24 ± 1.43 (2 h); 2.35 ± 1.30 (4 h); and 1.40 ± 1.09 (8 h). Tobramycin appears to be as effacacious as gentamicin in the treatment of serious
P. aeruginosa
infections and has a theoretical advantage of lower minimal inhibitory concentration for
P. aeruginosa
. The data suggest that, for life-threatening infections, dosages of tobramycin may need to be increased over those used in this study.
In Vitro Studies with Combinations of 5-Fluorocytosine and Amphotericin B
Authors: Shadomy Smith , Wagner Gerald , Espinel-Ingroff Ana , Davis Bettie A.
Published: June 2012

Synergistic antifungal activity of 5-fluorocytosine (5-FC) and amphotericin B was studied using an abbreviated checkerboard titration scheme. 5-FC was titrated in twofold increments (100 to 0.05 μg/ml) in the absence and presence of graded increments of amphotericin B (1.0. 0.5, 0.1, 0.05, and 0.01 μg/ml) in buffered yeast nitrogen base. A limited number of experiments were performed using expanded dual titration checkerboard schemes and growth curve studies. Forty-eight isolates of yeastlike organisms were tested; two were inhibited by the buffer system. Evidence of synergy, as indicated by a fourfold or greater reduction of the minimal inhibitory concentration of 5-FC in the presence of subinhibitory concentrations of amphotericin B, was seen with 11 of 46 isolates, or 24%, at the fungistatic level and with three isolates, or 7% at the fungicidal level. Indifferent results were obtained for 44 and 74% of the isolates, respectively, at the fungistatic and fungicidal levels. Antagonism was observed with three isolates.
Treatment of Influenza Infection of Mice by Using Rimantadine Hydrochlorides by the Aerosol and Intraperitoneal Routes
Authors: Stephen Edward L. , Dominik Joseph W. , Moe James B. , Spertzel Richard O. , Walker Jerry S.
Published: June 2012

Rimantadine hydrochloride was administered for 4 days in a small-particle (95% < 6.5 μm) aerosol (8.8 mg/kg per day) or intraperitoneally (40 mg/kg per day) to mice previously infected with influenza A/Aichi/2/68 (H
3
N
2
), mouse adapted. Mean time to death and incidence of survival were significantly increased in all treated groups of mice. The rate of eventual disappearance of virus from lung tissue was also accelerated by therapy. However, maximal mean virus titer per lung, and lung histopathology, did not reveal any difference between control and either group of treated mice. Aerosol therapy initiated at 72 h postinfection was as effective as that initiated at 6 h, even though lung virus titers of these mice had already peaked by 72 h. In contrast, intraperitoneal therapy initiated at 72 h was not effective in all studies.
Gentamicin Nephrotoxicity: Failure of Three Cephalosporins to Potentiate Injury in Rats
Authors: Harrison William O. , Silverblatt Fredric J. , Turck Marvin
Published: June 2012

The possibility that gentamicin and cephalosporin antibiotics may act synergistically to produce nephrotoxicity was evaluated in an experimental model. Necrosis of the proximal tubules occurred when rats were treated with 60 to 120 mg/kg of gentamicin for 5 days but not when 15 to 20 mg/kg per day was given for up to 4 weeks. In all gentamicin-treated animals lysosomes of proximal tubules were increased in size and number and the lumens of many tubules contained a granular deposit. Examination by electron microscopy revealed that the abnormal lysosomes contained membranous whorls. The luminal deposits consisted of similar material; identical bodies were also present in the urinary sediment. To determine whether concurrent administration of a cephalosporin would augment the nephrotoxic potential of gentamicin, additional rats were treated for 4 weeks with daily injections of gentamicin (20 mg/kg) and either cephaloridine, cephalothin, or cefazolin (500 mg/kg). None of the combination regimens produced any more injury than did gentamicin alone.
Concentration of Clindamycin in Human Bone
Authors: Nicholas Peter , Meyers Burt R. , Levy Roger N. , Hirschman Shalom Z.
Published: June 2012

Thirty patients undergoing total hip replacement received clindamycin beginning the day before surgery. Mean clindamycin concentrations during surgery were 7.33 ± 3.37 μg/ml in serum and 2.63 ± 1.76 μg/g in bone; mean ratio of bone-serum concentration was 0.40 ± 0.30.
Paradoxical Action of Penicillin G on
Staphylococcus aureus
: a Time Study of the Effect of a Zonal Antibiotic Concentration Gradient on Bacterial Growth
Authors: Yourassowsky E. , Vanderlinden M. P. , Lismont M. J. , Schoutens E.
Published: June 2012

The killing rate of a zonal concentration gradient of penicillin G on
Staphylococcus aureus
was studied by using a previously described triple-layer technique, enzymatic inactivation of the antibiotic, and an automatic image analyzer. This gradient determines a target image, whose center is the reservoir of antibiotic (constituted by a paper disk containing 100 U of penicillin G) and whose successive concentric zones are: a zone of slow bactericidal activity (corresponding to high levels of penicillin G), a zone of maximal bactericidal activity (corresponding to optimal levels of penicillin G), and a zone of overgrowth situated in front of the antibiotic wave.
Relation of Beta-Lactamase Activity to Antimicrobial Susceptibility in
Serratia marcescens
Authors: Tsang Joseph C. , Sansing Gerald A. , Miller Marcia A.
Published: June 2012

One-hundred clinical isolates of
Serratia marcescens
were tested for susceptibility to cephalothin, carbenicillin, ticarcillin, ampicillin, and cefoxitin. The majority of the 100 isolates (≥70%) were susceptible to carbenicillin, ticarcillin, and cefoxitin; less than one-half were susceptible to ampicillin; none were susceptible to cephalothin. Ten isolates from the 100 organisms tested were selectively assayed for their β-lactamase activity. Enzyme activity was measured using either iodometric or spectrophotometric methods, and the microbiological assay technique. It was concluded that β-lactamase production was not the sole determinant in β-lactam antibiotic resistance. Resistance without demonstrable β-lactamase was evident in strains for cephalothin, ampicillin, and cefoxitin. In addition, one strain which was susceptible to all antibiotics except cephalothin, elaborated considerable β-lactamase activity.
Effect of Inoculum and of Beta-Lactamase on the Anti-Staphylococcal Activity of Thirteen Penicillins and Cephalosporins
Authors: Sabath L. D. , Garner Carol , Wilcox Clare , Finland Maxwell
Published: June 2012

Because there are few persuasive data for selecting one semisynthetic penicillin or cephalosporin over another for treatment of serious staphylococcal infections, 118 recent clinical isolates of
Staphylococcus aureus
were studied to determine to what extent the presence of β-lactamase affected the relative anti-staphylococcal activity of six penicillins and seven cephalosporins. In addition, the effect of inoculum was studied for its possible effect on the anti-staphylococcal activity of the 13 β-lactam antibiotics. By all criteria, methicillin and nafcillin were clearly more resistant to both the inoculum effect and the production of staphylococcal β-lactamase, whereas benzylpenicillin and cephaloridine (especially benzyl-penicillin) were the most susceptible to these effects. Cephazolin was clearly more susceptible to staphylococcal β-lactamase and heavy inocula than the other cephalosporins (with the exception of cephaloridine), whereas cephalothin was the most resistant cephalosporin to these factors. The minimal inhibitory concentration for benzylpenicillin for tests with undiluted inoculum, compared to results with inoculum diluted 10
−4
, differed by a factor up to 16,384, whereas with methicillin and nafcillin the differences were rarely more than twofold. Ratios for the other 10 antibiotics fell between these extremes. These results suggest that methicillin or nafcillin is most stable to staphylococcal β-lactamase, and that benzylpenicillin and cephaloridine are the most susceptible.
Hospital
Pseudomonas aeruginosa
: Surveillance of Resistance to Gentamicin and Transfer of Aminoglycoside R Factor
Authors: Maliwan Nitaya , Grieble Hans G. , Bird Thomas J.
Published: June 2012

Tube dilution susceptibility tests in Trypticase soy broth showed that resistance to gentamicin (minimum bactericidal concentration ≧12.5 μg/ml) among hospital isolates of
Pseudomonas aeruginosa
increased from 13.9% in 1969 to 38.9% in 1972. Transfer of drug resistance to six aminoglycosides from one wild
Pseudomonas
strain to another was accomplished in recombination experiments. A carbenicillin-resistant, beta-lactamase-producing strain served as the recipient. The exconjugant was resistant not only to aminoglycosides, including amikacin, but also to all clinically employed antimicrobials. Aminoglycoside resistance in the exconjugant was cured by sodium dodecyl sulfate. This transferable aminoglycoside resistance was not mediated by adenylylation or, as judged by bioassay, by other antibiotic-inactivating or -modifying processes.