bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial Susceptibility of
Haemophilus parainfluenzae
Authors: Mayo Joan B. , McCarthy Laurence R.
Published: June 2012

Fifty random clinical isolates of
Haemophilus parainfluenzae
were tested for their susceptibility to 10 antibiotics by a microtiter broth dilution method. Three of the strains tested were resistant to ampicillin, whereas eight were resistant to tetracycline. All strains tested were susceptible to chloramphenicol, kanamycin, gentamicin, cephalothin, and colistin. The ranges of minimal inhibitory concentrations for the three remaining antibiotics were: 0.5 to ≥128 μg of penicillin G per ml, 0.03 to 4 μg of carbenicillin per ml, and 1 to 16 μg of erythromycin per ml. Elevated minimal inhibitory concentrations for penicillin and carbenicillin were noted for the three ampicillin-resistant strains. Tests for beta-lactamase production demonstrated the presence of this enzyme in each of the three ampicillin-resistant strains.
Tolerant Response of
Streptococcus sanguis
to Beta-Lactams and Other Cell Wall Inhibitors
Authors: Horne Diane , Tomasz Alexander
Published: June 2012

In contrast to group A streptococci or
Streptococcus pneumoniae
, cells of
Streptococcus sanguis
(group H) do not exhibit the irreversible effects of penicillin treatment, such as loss of viability or lysis. On the other hand, the same bacteria show typical effects of penicillin, such as morphological alterations, reduction in the rate of cell wall synthesis, and secretion of murein and lipoteichoic acid polymers into the medium. A novel effect of cell wall inhibitors was also noted: treatment with beta-lactams or with fosfomycin,
d
-cycloserine, or beta-halogeno-
d
-alanine caused the release of substantial amounts of glycerol lipids into the growth medium. The antibiotic “tolerance” of
S. sanguis
is interpreted in terms of the hypothesis that the activity of bacterial murein hydrolases is essential for the irreversible effects of cell wall inhibitors.
Rapid Penicillinase Paper Strip Test for Detection of Beta-Lactamase-Producing
Haemophilus influenzae
and
Neisseria gonorrhoeae
Authors: Jorgensen James H. , Lee Jean C. , Alexander Gary A.
Published: June 2012

A modified 1-min iodometric paper strip test for penicillinase activity was developed for detection of beta-lactamase-producing isolates of
Haemophilus influenzae
and
Neisseria gonorrhoeae
. The test is simple to perform and uses reagent-impregnated strips that may be stored for 1 year or more prior to use.
Pharmacokinetics and Tolerance of a Single Twelve-Tablet Dose of Trimethoprim (960 mg)-Sulfamethoxazole (4,800 mg)
Authors: Fass Robert J. , Prior Richard B. , Perkins Robert L.
Published: June 2012

To evaluate the potential usefulness of a single large oral dose of trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment of uncomplicated genitourinary gonorrhea, the pharmacokinetics of a 12-tablet dose containing 960 mg of TMP and 4,800 mg of SMZ were studied in 15 male volunteers, and the tolerance of this regimen was compared to that of a placebo in a double-blind crossover study. Both TMP and SMZ were rapidly absorbed. Peak mean serum concentrations (± standard deviation) of TMP, total SMZ, and free SMZ were 9.2 ± 2.2, 259.4 ± 40.9, and 233.7 ± 33.6 μg/ml, respectively. Elimination half-lives were 16.7, 14.6, and 12.9 h, respectively. When results were compared to data from similar studies after smaller doses, peak mean serum concentrations were proportional to dose, but elimination half-lives were longer after larger doses. Urinary concentrations of TMP, total SMZ, and free SMZ were many-fold higher than serum concentrations. Percents recovery (± standard deviation) in urine were 60.6 ± 10.6, 80.2 ± 7.8, and 37.4 ± 6.5%, respectively, during the 48 h after administration. The incidence of severe headache and of objective transient oliguria was significantly higher after TMP-SMZ than after placebo. Although the observed serum concentrations of TMP and SMZ surpassed concentrations necessary to inhibit clinical isolates of
Neisseria gonorrhoeae
in vitro for longer than 24 h, the adverse reactions associated with a 12-tablet dose of TMP-SMZ would preclude the clinical usefulness of such a therapeutic regimen.
Failure of Type 1 Herpesvirus to Develop Resistance to Ribavirin
Authors: Allen Lois B. , Fingal Christina M.
Published: June 2012

Exposure (10 passages) of type 1 herpesvirus to ribavirin or idoxuridine in Vero cells results in resistance to idoxuridine, but not to ribavirin.
Pharmacokinetic Study of Netilmicin
Authors: Meyers Burt R. , Hirschman Shalom Z. , Wormser Gary , Siegel David
Published: June 2012

Netilmicin at a dose of 2 mg/kg was infused intravenously into 10 healthy volunteers. A peak serum concentration of 16.56 μg/ml was obtained at the end of the infusion. Thirty-nine percent of the infused dose was excreted in the urine during the first 8 h after infusion. The pharmacokinetic parameters of netilmicin were derived by analyzing the elimination data according to a two-compartment model.
Cefuroxime, a New Parenteral Cephalosporin: Collaborative In Vitro Susceptibility Comparison with Cephalothin Against 5,887 Clinical Bacterial Isolates
Authors: Jones Ronald N. , Fuchs Peter C. , Gavan Thomas L. , Gerlach E. Hugh , Barry A. L. , Thornsberry Clyde
Published: June 2012

Cefuroxime, a new parenteral cephalosporin was compared with cephalothin by broth microdilution susceptibility testing against 5,887 routine clinical bacterial isolates in four large clinical laboratories. The minimal inhibitory concentrations (MICs) of cefuroxime against the
Enterobacteriaceae
were consistently lower than those of cephalothin. This was most striking among the
Enterobacter
species, which were generally susceptible to cefuroxime (MIC ≤ 8 μg/ml), but resistant to cephalothin. Similar results occurred with
Haemophilus
species,
Acinetobacter anitratus
, meningococci, and
Aeromonas hydrophilia
, but
Pseudomonas
species and enterococci were resistant to high concentrations of both drugs. Streptococci showed slightly greater susceptibility to cefuroxime than to cephalothin. By contrast, staphylococci were more susceptible to cephalothin.
Bacteroides fragilis
was resistant to cefuroxime, but other anaerobes were generally susceptible.
Pharmacokinetics of Nafcillin in Patients with Renal Failure
Authors: Diaz Carlos R. , Kane James G. , Parker Richard H. , Pelsor Frank R.
Published: June 2012

Nafcillin, a pencillinase-resistant penicillin, is frequently used for treatment of staphylococcal infections in hemodialysis patients. Despite its widespread use, there is a paucity of available data regarding the pharmacokinetics of nafcillin in hemodialysis patients. Therefore, sodium nafcillin, 25 mg/kg, was given intravenously over a 5- to 15-min period to 12 hemodialysis patients. Eleven patients were studied during dialysis, and eight of these were studied again during the interdialysis period. The initial serum half-life for nafcillin was 0.208 h during dialyses and 0.278 h between dialyses. The terminal half-life was 1.48 h during dialyses and 1.89 h between dialyses. There was no statistically significant difference between these values. These data indicate that renal failure does not appreciably affect the serum half-life of nafcillin, and hemodialysis does not accelerate the rate of clearance of nafcillin from the blood. Therefore, no modification of the usual nafcillin dosage is necessary when using this drug in hemodialysis patients.
Specificity of Isoniazid on Growth Inhibition and Competition for an Oxidized Nicotinamide Adenine Dinucleotide Regulatory Site on the Electron Transport Pathway in
Mycobacterium phlei
Authors: Davis William B. , Weber Morton M.
Published: June 2012

The mechanism of action of isoniazid (INH) on saprophytic and atypical mycobacteria is thought to be different from that on
Mycobacterium tuberculosis
because higher concentrations are required to be effective in these species. In this investigation,
M. phlei
was inhibited by INH at a concentration of 25 μg/ml. Benzoic acid hydrazide (BZH) and nicotinic acid hydrazide (NAH) were inhibitory at levels of 300 and 500 μg/ml, respectively. Inhibition by these compounds was not inoculum dependent. An isolated
M. phlei
mutant resistant to 100 μg of INH per ml (Inh
r
) was inhibited by INH only at concentrations about equal to those inhibitory for BZH and NAH. When NAH and BZH were below their minimal inhibitory concentrations, INH inhibition was antagonized. Hence, there appears to be a single target site for INH in mycobacteria with different affinities for various hydrazide analogs of INH. The increased inhibitory levels required for the atypical and saprophytic species are due to a decreased affinity of the target site for INH in these species. INH also inhibited both the oxidized nicotinamide adenine dinucleotide (NAD
+
) and adenosine 5′-monophosphate stimulation of reduced NAD (NADH) oxidase activity associated with the
M. phlei
and
M. tuberculosis
H
37
R
a
electron transport particles. INH did not reverse the NAD
+
stimulation of oxidase activity in the Inh
r
strain of
M. phlei
. No direct inhibitory effect of INH on NADH oxidase activity was observed. Incubation of
M. phlei
electron transport particles at 0°C with INH resulted in a dramatic loss of oxidase activity which could have been prevented if NAD
+
were present. However, INH had no effect upon the NADH oxidase when stored with electron transport particles isolated from the Inh
r
strain. Therefore, INH inhibition of regulation and/or stabilization of the electron transport pathway by NAD
+
or adenosine 5′-monophosphate may account, in part, for the lethal action of the drug on mycobacteria.
Morphological Changes in Yeasts as a Result of the Action of 5-Fluorocytosine
Authors: Arai Tadashi , Mikami Yuzuru , Yokoyama Koji , Kawata Tomio , Masuda Kuniyoshi
Published: June 2012

The mode of action of 5-fluorocytosine on
Candida albicans
and
Saccharomyces cerevisiae
was studied with special reference to morphology and ultrastructure. Shortly after contact of yeast cells with 10 μg of 5-fluorocytosine per ml, marked enlargement of the cells occurred. The initial increase in cell size was almost the same with both yeast strains. As incubation proceeded, further increase in cell volume continued with
C. albicans
, whereas no further change in cell volume was observed with
S. cerevisiae
. An electron microscope examination of
C. albicans
cells after exposure to the drug revealed characteristic changes, consisting of an enlarged nucleus and a thin cell wall. The morphological changes were exactly comparable to those reported with inhibitors of deoxyribonucleic acid synthesis in mammalian cells and some bacteria.
Comparative Stability of Cephalothin and Cefazolin in Buffer or Human Serum
Authors: Pitkin Donald , Actor Paul , Filan John J. , White Roderick , Weisbach Jerry A.
Published: June 2012

A marked loss in potency was observed when cephalothin was incubated for 5 h in human serum at 37°C. Cefazolin was stable under these conditions.
Detection of Antimetabolite Activity: Effects and Transport of Tryptophan Analogs in
Escherichia coli
Authors: Kuhn Jonathan
Published: June 2012

Simple and rapid techniques were developed that allow detection of the effects of a wide range of tryptophan analogs in
Escherichia coli
. (i) By using certain supersensitive mutant strains, analogs that were without effect on a wild-type strain were shown to be inhibitory. (ii) Many other analogs could inhibit the utilization of
d
-tryptophan when present as
l
-tryptophan replacements in a
trp dadR
strain. (iii) Another approach was to test the ability of a given analog to reverse the inhibition caused by an inhibitory analog. These combined approaches revealed activities in 26 analogs out of a total of 40 that were inactive by testing solely on a wild-type strain. The route of entry of inhibitory analogs was determined unambiguously by comparing their effect on
aroP
+
(aromatic permease) and
aroP
strains. Uptake studies were also performed to determine whether various analogs compete for entry via the aromatic permease system. Many tryptophan analogs enter the cell via this system. The methods developed here should have general applicability to the testing of analogs of a variety of other metabolites.
Enhancement of Antistaphylococcal Activity of Nafcillin and Oxacillin by Sisomicin and Netilmicin
Authors: Watanakunakorn Chatrchai , Glotzbecker Cheryl
Published: June 2012

The in vitro activity of sisomicin, netilmicin, nafcillin, and oxacillin against 35 strains of
Staphylococcus aureus
isolated from blood cultures of patients with endocarditis or septicemia was studied. The effects of combinations of either of the two newer aminoglycosides and either of the two penicillinase-resistant penicillins on the killing of
S. aureus
were investigated. All
S. aureus
strains were susceptible to the four antibiotics. Enhancement of antistaphylococcal activity was demonstrated by the antibiotic combinations.
Resistance to Six Aminoglycosidic Aminocyclitol Antibiotics Among Enterococci: Prevalence, Evolution, and Relationship to Synergism with Penicillin
Authors: Calderwood Susan Adams , Wennersten Christine , Moellering Robert C. , Kunz Lawrence J. , Krogstad Donald J.
Published: June 2012

Two hundred and three recent clinical isolates of enterococci were tested for susceptibility to streptomycin, kanamycin, amikacin, gentamicin, sisomicin, and tobramycin. Depending upon the source of the isolate, 36 to 54% of the enterococci demonstrated high-level resistance (minimal inhibitory concentration, >2,000 μg/ml) to streptomycin, 16 to 49% to kanamycin, and 0 to 14% to amikacin. None of the strains was highly resistant to gentamicin, sisomicin, or tobramycin. A comparison with isolates of enterococci obtained in 1968 revealed that there has been a decrease in prevalence of high-level resistance among organisms isolated from wound cultures in 1976. However, no decrease in resistance to streptomycin or kanamycin was demonstrated among blood or urine isolates. Penicillin, combined with gentamicin, sisomicin, or tobramycin, was synergistic against all 10 strains of
Streptococcus faecalis
subjected to formal testing. For streptomycin and kanamycin, the presence or absence of synergism with penicillin correlated with the absence or presence of high-level aminoglycoside resistance. High-level resistance to amikacin was seen in only 1 of the 10 strains. Nonetheless, combinations of penicillin plus amikacin failed to produce synergistic killing against 6 of the 10 strains. Indeed, the combination was synergistic only against those four strains that were susceptible to high levels of kanamycin.
Elimination of Plasmids from Several Bacterial Species by Novobiocin
Authors: McHugh Gail L. , Swartz Morton N.
Published: June 2012

Certain plasmids can be eliminated by exposure to growth-inhibiting concentrations of novobiocin. Novobiocin cured 8 of 14 plasmids (13 R-plasmids and an F′
lac
) among one or another of four different bacterial hosts.
In Vitro and In Vivo Antibacterial Activity of T-1220, a New Semisynthetic Penicillin
Authors: Ueo K. , Fukuoka Y. , Hayashi T. , Yasuda T. , Taki H. , Tai M. , Watanabe Y. , Saikawa I. , Mitsuhashi S.
Published: June 2012

T-1220, sodium 6-[
d
-(-)-α-(4-ethyl-2,3-dioxo-1-piperazinylcarbonyl-amino)- α-phenylacetamido] penicillanate, is a new semisynthetic penicillin derivative that possesses a broad spectrum of in vitro antibacterial activity against gram-positive and gram-negative bacteria. T-1220 is more effective than carbenicillin (CB-PC) against
Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus
species, and
Serratia marcescens
. Addition of human serum to culture media did not significantly alter the antibacterial activity of T-1220. Greater bactericidal activity toward various strains of gram-negative bacteria was demonstrated with T-1220 than with CB-PC. T-1220, like penicillin G, was hydrolyzed by penicillinase, but was sable to a type IV penicillinase produced by
P. aeruginosa
strains. In vivo antibacterial activities of T-1220, ampicillin (AB-PC), and CB-PC were compared, using systemic infections of mice with
P. aeruginosa, K. pneumoniae
, and
Escherichia coli
. The 50% effective doses (milligrams per kilogram) of T-1220 were consistently lower than those of AB-PC and CB-PC.
Clinical and Bacteriological Evaluation of Netilmicin in Gram-Negative Infections
Authors: Klastersky J. , Meunier-Carpentier F. , Coppens-Kahan L. , Daneau D. , Prevost J. M.
Published: June 2012

A preliminary study was conducted with netilmicin, a new aminoglycoside antibiotic. Its effectiveness was evaluated in vitro against 546 strains of
Enterobacteriaceae
and
Pseudomonas aeruginosa
isolated from clinical material. Its effectiveness against gentamicin-susceptible strains was roughly similar to that of gentamicin and other newer aminoglycoside antibiotics. Cross-resistance to netilmicin was found in 9 of 44 gentamicin-resistant strains. A favorable clinical response was observed in 70% of the patients treated with a dose of netilmicin ranging from 4.5 to 7.5 mg/kg. However, the appearance of granular casts was seen in 7 of 10 patients receiving the higher dosage of netilmicin (7.5 mg/kg) and a rise in blood urea nitrogen or serum creatinine levels was observed in 5 of these patients.
Inactivation and Inhibition of Replication of the Enveloped Bacteriophage φ6 by Fatty Acids
Authors: Sands Jeffrey A.
Published: June 2012

The enveloped bacteriophage φ6 has been shown to be an interesting model system for the study of chemical agents that might have specific antiviral effects against lipid-containing mammalian viruses. In this report, we describe two types of antiviral activity exhibited by several fatty acids against bacteriophage φ6. Oleic acid (18:1) and palmitoleic acid (16:1) were potent inactivators of the virus. Treatment with either fatty acid at 50 μg/ml at 25 or 0°C for 30 min reduced the virus titer to about 0.1% of the initial titer. Oleic acid at a concentration as low as 3 μg/ml (∼10
−2
mM) reduced the virus titer to <1% of the initial titer within 30 min. Ultracentrifugation analyses of
14
C-amino acid- and
32
P-labeled virus treated with oleic acid indicated that the virion is largely disassembled by the treatment. Myristic acid (14:0) and palmitic acid (16:0) did not inactivate φ6 at 50 μg/ml, but nevertheless did prevent φ6 plaque production. Single-step virus growth experiments in which fatty acid was added at various times before or after infection indicated that it was an early stage of the φ6 replication cycle that was inhibited by the presence of myristic acid and that the inhibition occurred only if the myristic acid concentration in the extracellular growth medium was ≳10 μg/ml. φ6 could attach to its host cell in the presence of myristic acid at 50 μg/ml. We conclude that the fatty acids that prevent φ6 replication probably do so by interfering with the entry of the viral genome into the host cell.
Agar Shake Tube Technique for Simultaneous Determination of Aerobic and Anaerobic Susceptibility to Antibiotics
Authors: Evans James B. , Harrell Lizzie J.
Published: June 2012

The broth dilution method of determining the minimum inhibitory concentration (MIC) of antibiotics has been adapted to an agar shake tube technique with semisolid media. This permits the simultaneous determination of the aerobic and anaerobic MICs for facultatively anaerobic bacteria such as staphylococci.
Antibiotic Resistance Patterns of Metal-Tolerant Bacteria Isolated from an Estuary
Authors: Allen D. A. , Austin B. , Colwell R. R.
Published: June 2012

Estuarine bacteria isolated on metal-containing media were also found to be antibiotic resistant; ampicillin and chloramphenicol were the antibiotics to which resistance was most common. Patterns of antibiotic resistance were found associated with a variety of taxa.
Gentamicin and Tobramycin Penetration into Synovial Fluid
Authors: Dee Thomas H. , Kozin Franklin
Published: June 2012

The penetration of gentamicin and tobramycin into the synovial fluid of 12 patients with nontraumatic joint effusions was studied. Simultaneous serum and synovial fluid specimens taken after the intramuscular or intravenous administration of an antimicrobial agent were assayed. Synovial fluid levels of antibiotic were >50% of serum levels in all subjects studied. In five patients, synovial fluid levels were equal to or exceeded simultaneous serum values. These results suggest that intra-articular injection of aminoglycoside antibiotics is not necessary in the treatment of infectious arthritis.
Growth Properties of Mecillinam-Resistant Bacterial Variants in Urine
Authors: Anderson J. D. , Adams M. A. , Webster H. M. , Smith L.
Published: June 2012

Resistant variants are often formed when susceptible
Enterobacteriaceae
are grown in media containing mecillinam. These variants have not yet been detected in patients or identified as a cause of treatment failure in limited clinical trials. Mecillinam-resistant organisms were formed by 5 out of 13 urinary isolates of
Enterobacteriaceae
incubated in urine containing mecillinam. The mean generation time of these five variants in urine containing therapeutic concentrations of mecillinam was 3.2 times that of normal organisms in antibiotic-free urine. When three of these five resistant variants were subcultured in antibiotic-free urine, the generation time, morphology, and antibiotic susceptibility returned to normal. On antibiotic-free agar medium, all five mecillinam-resistant variants readily reverted to the “susceptible” form and were therefore more likely to be phenotypic rather than genotypic mutants. In a second series of experiments, the flushing effect of the bladder on the clearance of organisms was partly simulated by frequent subculture in urine. Under these conditions, the cell density of cultures of all bacteria remained high during 10 subcultures over 52 h. However, bacterial populations progressively decreased in urine containing mecillinam until none could be detected at 28 h or thereafter. The slow growth rate of mecillinam-resistant variants may explain why detectable numbers of these organisms fail to colonize the urinary tract during treatment. Other factors may reinforce the postulated effect of the reduced growth rate in vivo.
Comparative Pharmacology of Amphotericin B and Amphotericin B Methyl Ester in the Non-Human Primate,
Macaca mulatta
Authors: Jagdis F. A. , Hoeprich P. D. , Lawrence R. M. , Schaffner C. P.
Published: June 2012

The pharmacokinetics of amphotericin B methyl ester hydrochloride (AME) and commercial deoxycholate-stabilized amphotericin B (AMB) were compared after single doses of 5 mg and 1 mg/kg of body weight, respectively, given intravenously in a period of 3 h to adult female rhesus monkeys (
Macaca mulatta
). By bioassay, the concentrations of AME were 12.2 to 7.2 times higher in the serum and 7.8 to 2.5 times higher in the urine during the 8 h after infusion. The decline in concentrations of the drugs in sera was consistent with a three-compartment, open pharmacokinetic model; rate constants of transfer of the drugs between the compartments and volumes of distribution were calculated. The overall rate of elimination from the central compartment (the bloodvascular space) was about four times greater for AME than for AMB. Serum urea nitrogen and creatinine concentrations were mildly and transiently increased after infusion of AME, whereas the more severe azotemia that followed infusion of AMB persisted for 5 days. AME was less toxic and achieved a greater urinary outfall than AMB. As the antifungal activity of AME is comparable to that of AMB by testing in vitro, further study is warranted.
Systemic Metabolic Alterations Associated with Repeated Injections of a Modified Polyriboinosinic-Polyribocytidylic Acid Complex
Authors: Powanda Michael C. , Sammons Myrl L. , Stephen Edward L.
Published: June 2012

Polyriboinosinic acid-polyribocytidylic acid complexed with poly-1-lysine and injected intramuscularly into rats (0.3 or 3.0 mg/kg) produced fever, altered leukocyte count, slightly depressed plasma zinc, increased amino acid uptake into liver, and increased plasma acute-phase globulins two- to threefold. It is suggested that these systemic metabolic alterations are indicative of a mild inflammatory response to this drug. The metabolic alterations may have to be taken into consideration when polyriboinosinic acid-polyribocytidylic acid complexed with poly-1-lysine is used in therapy.
Gentamicin Intravenous Infusion Rate: Effect on Interstitial Fluid Concentration
Authors: Kozak Alan J. , Gerding Dale N. , Peterson Lance R. , Hall Wendell H.
Published: June 2012

To assess the possible role of intravenous (i.v.) infusion rate as a determinant of degree and rate of interstitial fluid penetration, six rabbits, each with four intraperitoneal implanted capsules, were studied by crossover design after a single dose of 1.7 mg of gentamicin per kg by either slow 2.5-min i.v. bolus or 30 min i.v. infusion. The mean serum peak antibiotic level after slow bolus was 17.4 μg/ml. After 30 min of infusion, mean serum peak was 8.3 μg/ml (
P
< 0.025). Mean capsule fluid antibiotic levels at 30 min, 1, and 2 h were 0.9 μg/ml, 1.6 μg/ml, and 1.8 μg/ml, respectively, after slow bolus and 0.6 μg/ml, 0.9 μg/ml, and 1.3 μg/ml after 30-min infusion (
P
< 0.05 at 30 min,
P
< 0.001 at 1 h, and
P
< 0.05 at 2 h). Comparison of capsule levels beyond 2 h revealed no significant differences, and peak capsular concentrations achieved by the two methods were similar. Slow 2.5-min i.v. bolus administration of gentamicin established higher interstitial fluid levels during the first 2 h of therapy and may be the preferred mode of delivery when rapid extravascular penetration is desired.
Blood, Brain, and Cerebrospinal Fluid Concentrations of Several Antibiotics in Rabbits with Intact and Inflamed Meninges
Authors: Beam Thomas R. , Allen James C.
Published: June 2012

Because cerebrospinal fluid (CSF) antibiotic levels fail to predict either clinical success or relapse in the treatment of bacterial meningitis, we examined simultaneous antibiotic concentrations in the blood, brain, and CSF of control rabbits and of animals with experimental pneumococcal meningitis. Cefamandole pharmacokinetics were analyzed in detail and compared with those of cephalothin, ampicillin, penicillin G, and tobramycin. After 4 h of continuous intravenous infusion, cefamandole reached concentrations in both brain and CSF in excess of the minimal bactericidal concentration for the test organism and compared favorably with ampicillin and penicillin in achieving bacteriological cure. Cephalothin levels in the central nervous system remained undetectable in both control and infected animals during this time. Tobramycin concentrations were measurable in the CSF, but not in brain tissue in association with an inflammatory stimulus.
Structural Requirements of Guanide, Biguanide, and Bisbiguanide Agents for Antiplaque Activity
Authors: Tanzer J. M. , Slee A. M. , Kamay B. A.
Published: June 2012

The bactericidal efficacy of 16 guanide, biguanide, and bisbiguanide agents was studied in vitro against intact preformed plaques of four oral (plaque-forming) microorganisms:
Streptococcus mutans, S. sanguis, Actinomyces viscosus
, and
A. naeslundii
. The activities of these agents were examined in relation to their molecular configurations. These studies indicated that the bis- and biguanide configurations are important for efficacy, as is the length of the alkyl side chain. No structural moiety determined efficacy by itself. Furthermore, the activities of these agents were studied to determine the minimal conditions (concentration, duration, and frequency) of treatment required for likely clinical efficacy. At least six agents were judged to have equal or greater efficacy than the reference agent, chlorhexidine digluconate. A plaque bactericidal index was derived for the most potent agents, and comparison to the bactericidal properties of chlorhexidine was expressed as a chlorhexidine coefficient.
Effect of Metronidazole on the Intestinal Microflora of the American Cockroach,
Periplaneta americana L
Authors: Bracke J. W. , Cruden Diana Loeb , Markovetz A. J.
Published: June 2012

The effect of feeding to cockroaches the antimicrobial agent metronidazole, which acts specifically against anaerobes, was assessed by light and scanning electron microscopy, bacteriological examination, and methane formation. Types of organisms and total numbers were greatly reduced from controls. The health of mature adults was unaffected, but stunting occurred in subadult animals maintained on the antibiotic from hatching. The intracellular bacteria of the fat body were not affected by the drug. The results are discussed with respect to a proposed microbe-host extracellular symbiosis.
SCE-129, Antipseudomonal Cephalosporin: In Vitro and In Vivo Antibacterial Activities
Authors: Tsuchiya Kanji , Kondo Masahiro , Nagatomo Hiroshi
Published: June 2012

SCE-129 [3-(4-carbamoyl-1-pyridiniomethyl)-7β-(
d
-α-sulfophenylacetamido)-ceph-3-em-4-carboxylate monosodium salt], a new semisynthetic cephalosporin, shows potent in vitro antibacterial activities against
Pseudomonas aeruginosa
and some gram-positive bacteria, whereas it shows lower activity against many gram-negative rods. Against clinical isolates of
P. aeruginosa
this cephalosporin exhibited higher activity than did carbenicillin, and against the strains of
Staphylococcus aureus
, SCE-129 had similar activity to carbenicillin. Variations in pH, addition of horse serum, and type of growth medium had no significant effects on the activity of the cephalosporin; however, the inoculum size had some effect on the activity. SCE-129 is an effective bactericidal agent against
P. aeruginosa
and
S. aureus
. The protective effects of SCE-129 in mice infected with
P. aeruginosa
and
S. aureus
were more potent than those of carbenicillin. The protective effects of SCE-129 on
Pseudomonas
infection in mice varied according to the dosage schedule and the challenge dose. In a multiple dose schedule, a smaller amount of SCE-129 was necessary than that in a single dose schedule. The effects of SCE-129 after subcutaneous or intraperitoneal administration were more potent than were those by intravenous administration. No protective effect was observed by oral administration.
Reversible Inhibition of Cellular Metabolism by Ribavirin
Authors: Larsson Alf , Stenberg Kjell , Öberg Bo
Published: June 2012

The broad spectrum antiviral drug ribavirin (Virazole, 1-β-
d
-ribofuranosyl-1,2,4-triazole-3-carboxamide) inhibits cellular macromolecular synthesis as well as cell division in eucaryotic cells. The concentration and time dependence have been studied. One-hour treatment with 25 μM ribavirin or 18 h with 2 μM inhibited the deoxyribonucleic acid synthesis to 50%. Higher concentrations of ribavirin were required to obtain a similar inhibition of ribonucleic acid and protein synthesis. This effect on cell metabolism and cell division can be reversed by removing the drug from the cells.
Use of High-Pressure Liquid Chromatography to Determine Plasma Levels of Metronidazole and Metabolites After Intravenous Administration
Authors: Wheeler L. A. , De Meo M. , Halula M. , George L. , Heseltine P.
Published: June 2012

A rapid and sensitive high-pressure liquid chromatography assay for metronidazole and its two principle metabolites, 1-(2-hydroxyethyl-2-hydroxymethyl)-5-nitro-imidazole [hydroxy metabolite] and 1-acetic acid-2-methyl-5-metronidazole [acid metabolite], was developed. The retention times observed were 5.7, 3.3, and 4.5 min, respectively. A reverse-phase μC
18
Bondapak column using a solvent system of methanol, acetonitrile, and 0.005 M pH 4 potassium dihydrogen phosphate (4:3:93, vol/vol) was used to achieve separation of the three compounds. Patients receiving metronidazole therapy were given a loading dose of 13.6 mg of drug per kg intravenously over 1 h, followed by a maintenance dose of 1.43 mg/kg per h. The range of metronidazole concentrations observed was 6.8 to 47.5 μg/ml. These levels are well above the minimal inhibitory concentrations of most clinically significant anaerobic bacteria including
Bacteroides fragilis
. Little of the acid metabolite was observed in the plasma. The concentration of hydroxy metabolite ranged from 1.6 to 16 μg/ml. The latter may represent an additional source of antimicrobial activity since the hydroxy metabolite has approximately 30% the biological activity of metronidazole.
Gentamicin Use and
Pseudomonas
and
Serratia
Resistance: Effect of a Surgical Prophylaxis Regimen
Authors: Roberts Norbert J. , Douglas R. Gordon
Published: June 2012

An outbreak of prosthetic valve endocarditis due to methicillin-resistant
Staphylococcus epidermidis
prompted a change in antimicrobial prophylaxis for open heart surgery in a general hospital from a regimen of aqueous penicillin G, methicillin, and kanamycin to a 5-day regimen of cefazolin and gentamicin. As a result, total gentamicin use in the hospital more than doubled. Increased resistance of pseudomonas and serratia isolates paralleled the increased total use of gentamicin. For pseudomonas species, the incidence of gentamicin resistance increased from 3 to 15%; for serratia species, from 8 to 88%; and for the total of both organisms, from 4 to 28%. Resistance decreased rapidly after removal of gentamicin from the prophylaxis regimen. Review of serratia isolates from the urinary tract showed that gentamicin resistance was associated with prior antibiotic therapy, especially with gentamicin, care on the surgical services, especially the surgical intensive care unit, and presence of indwelling bladder catheters. Gentamicin use in a 5-day antimicrobial prophylaxis regimen for open heart surgery can represent a large proportion of the total hospital use of that antibiotic, with potential adverse effects on hospital flora.
Quantitation of Antibiotics by High-Pressure Liquid Chromatography: Cephalothin
Authors: Nilsson-Ehle Ingrid , Yoshikawa Thomas T. , Schotz Michael C. , Guze Lucien B.
Published: June 2012

A technique for quantitative determination of cephalothin and desacetylcephalothin in serum using a method based on high-pressure liquid chromatography is described. Both compounds were quantitatively extracted from serum by using dimethylformamide. After separation of the drugs by reverse-phase chromatography and detection by ultraviolet light absorption at 254 nm, serum concentrations of cephalothin and desacetylcephalothin as low as 1.0 μg/ml were measured. No interfering absorption was found in extracts of serum samples from normal humans or patients receiving a variety of other drugs, including other antimicrobial agents. Serum specimens obtained after an intravenous infusion of cephalothin to two human subjects and three dogs were assayed by the chemical and microbiological assays. When values, as determined by the chemical method and the microbiological assay in samples from human subjects, were compared, the correlation coefficient (
r
) was 0.96, whereas, in the dogs, the
r
value was 0.79. The chemical procedure described in this report for determination of cephalothin and desacetylcephalothin permits future pharmacokinetic investigations of these compounds. This assay is sensitive, specific, accurate, and rapid (approximately 30 min), and appears suitable for routine clinical use.
Treatment of Experimental Murine Cryptococcosis: a Comparison of Miconazole and Amphotericin B
Authors: Graybill John R. , Mitchell Linda , Levine Hillel B.
Published: June 2012

Miconazole was compared with amphotericin B in the treatment of murine cryptococcosis. Both subcutaneous and intraperitoneal administration of miconazole produced serum levels higher than the minimum inhibitory concentration for the challenge strain. However, maximal tolerable doses of miconazole gave no increase in survival. When combined with amphotericin B, miconazole demonstrated neither additive nor antagonistic effects on survival. Spleen and brain counts of cryptococci were not lowered by miconazole; also, miconazole did not alter the effect of amphotericin B on reducing tissue counts. In vitro studies confirmed that the strain of
Cryptococcus neoformans
was quite susceptible to both miconazole and amphotericin B. However, miconazole had a delayed onset of antifungal activity. This was apparent even at miconazole levels 20 times greater than the minimum inhibitory concentration. Also, the antifungal activity of miconazole was markedly inhibited by serum. Delayed antifungal activity and serum inhibition may limit the in vivo effectiveness of miconazole in murine cryptococcosis.
Activity of Amantadine, Rimantadine, and Ribavirin Against Swine Influenza in Mice and Squirrel Monkeys
Authors: Scott G. H. , Stephen E. L. , Berendt R. F.
Published: June 2012

Amantadine, rimantadine, and ribavirin given orally, either prophylactically or therapeutically, reduced mortality and increased the survival time of 3-week-old mice infected with the type A/New Jersey/8/76 (swine) strain of influenza virus. In addition, amantadine and rimantadine, administered therapeutically, increased the rate of virus clearance from lungs of infected mice. Administration of amantadine either before or after virus challenge ameliorated the illness in squirrel monkeys; when administered therapeutically, it appeared to eliminate virus shedding from infected monkeys within hours after therapy was initiated.
In vitro and in vivo studies with BL-S786, cefoxitin, and cefamandole
Authors: Shadomy S , Wagner G , Carver M
Published: June 2012

The in vitro antimicrobial activities of BL-S786, cefoxitin, and cefamandole against 90 isolates of Enterobacteriaceae, including Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae and E. aerogenes, were studied by using an agar dilution procedure. Comparison of geometric mean minimal inhibitory concentrations showed that BL-S786 was half as active as cefamandole against Enterobacter species, 2 to 4 times more active than cefamandole against all other species, and 4 to 25 times more active than cefoxitin against all species. In vivo experiments employed acute protection tests in infected mice, using five isolates each of the five genera. Drugs were administered intramuscularly in two doses 3 h apart at dosages of 2.5, 5, 10, 20, and 40 mg per mouse. In most instances, BL-S786 was the most efficacious drug, being some 1.3 to 9.1 times more active than cefoxitin in all experiments and 1.5 to 8.7 times more active than cefamandole in most experiments. BL-S786 and cefamandole were comparable in activity in experiments with E. aerogenes, whereas BL-S786 was superior in experiments with E. cloacae.
Target substances of some antifungal agents in the cell membrane
Authors: Kuroda S , Uno J , Arai T
Published: June 2012

Copiamycin, an antifungal antibiotic, exhibits antimicrobial activity against a few bacteria in addition to a wide variety of fungi. The methanol extract of Sarcina lutea, one of the most susceptible bacteria, was found to reverse the antimicrobial activity of copiamycin. The reversing activity was associated with the phospholipid fraction of the bacteria. The S. lutea phospholipids also reversed the activities of azalomycin F and miconazole, but not that of clotrimazole. The effects of authentic phospholipids and fatty acids were also investigated. As the antimicrobial activities of copiamycin and azalomycin F were most strongly reversed in the same manner by phospholipids with unsaturated fatty acids and basic hydrophilic groups, the sites on the cell membrane sensitive to both antibiotics are assumed to be identical. On the other hand, the activity of miconazole was affected by different phospholipids from those which affected these two antifungal antibiotics, and the activity of clotrimazole was not affected by any of the phospholipids and fatty acids. It was postulated that the sites on the cell membrane sensitive to miconazole and clotrimazole are different from those sensitive to copiamycin and azalomycin F.
Infections due to gentamicin-resistant Staphylococcus aureus strain in a nursery for neonatal infants
Authors: Vogel L , Nathan C , Sweeney H M , Kabins S A , Cohen S
Published: June 2012

An apparently homogeneous strain of Staphylococcus aureus resistant to gentamicin (Gmr), kanamycin, tobramycin, and sisomicin, but susceptible to amikacin and netilmicin, caused multiple infections in neonatal infants in a special care nursery. Nasal cultures revealed a high rate of carriage of the Gmr staphylococcus in infants without clinical infection. Segregating patients according to a modified cohort system and use of careful aseptic techniques led to apparent elimination of the Gmr strain. The resistance to aminoglycosides in this strain was mediated by an aminoglycoside 6'-N-acetyltransferase and a gentamicin phosphotransferase. Genetic determinants for these enzymes were borne on a circular covalently closed plasmid of approximately 11 megadaltons. These resistance determinants closely resemble those found in isolates of S. aureus that have caused nosocomial infections in patients in Europe.
In vitro antimicrobial activity of some cyclic hydroxamic acids and related lactams
Authors: Davis A L , Hulme K L , Wilson G T , McCord T J
Published: June 2012

Against Enterobacter aerogenes 13048, Serratia marcescens 13880, Klebsiella pneumoniae 10031, Pseudomonas aeruginosa 10145, Escherichia coli 9723, Lactobacillus casei 7469, Lactobacillus plantarum 8014, Leuconostoc dextranicum 8086, and Streptococcus faecalis 8043, the mean minimal inhibitory concentrations of three cyclic hydroxamic acids, 3-amino-3,4-dihydro-1-hydroxycarbostyril, the 6-chloro analog, and the 7-chloro analog, were 0.6, 0.6, and 0.2 micrograms/ml, and those of the corresponding lactams, 3-amino-3,4-dihydrocarbostyril, the 6-chloro analog, and the 7-chloro analog, were 60, 60, and 6 micrograms/ml, respectively. Under the same assay conditions the mean minimal inhibitory concentrations of chloramphenicol and kanamycin were both 2 micrograms/ml. In addition, the cyclic hydroxamic acids but not the lactams inhibited the growth of Candida albicans at minimal inhibitory concentrations ranging from 20 to 200 micrograms/ml, at pH 7, as compared with that of amphotericin B, at 2 micrograms/ml.
Stability of Antibiotics and Amino Acids in Two Synthetic
l
-Amino Acid Solutions Commonly Used for Total Parenteral Nutrition in Children
Authors: Colding Hanne , Andersen Gunnar Eg
Published: June 2012

The stability and interaction at 29°C of ampicillin, carbenicillin, gentamicin, and polymyxin B were examined in a common electrolyte solution, invertose darrow, and in two synthetic
l
-amino acid solutions, one commercial (vamin with fructose; Vitrum) and the other a neonatal preparation modified for use in newborn infants. The concentration of amino acids was measured before and after the addition of these antibiotics. The concentration of antibiotics was measured over a 24-h period with a microbiological method. The concentration of ampicillin in invertose darrow fell 52%, and in vamin with fructose it fell 69%, whereas in the neonatal preparation the fall was only 22%. The concentration of carbenicillin in vamin with fructose fell 37%, and in the neonatal preparation it fell 31%. The combination of ampicillin or carbenicillin with gentamicin or polymyxin B did not influence the activity of the penicillins. The concentration of gentamicin and polymyxin B was unchanged in all solutions over a 24-h period. With the exception of cystine, the concentration of all amino acids remained constant after 24 h in the neonatal preparation with and without the different combinations of antibiotics. For cystine there was a fall of 20 to 30%.
Human Leukocyte Interferon in the Treatment of Varicella in Children with Cancer: a Preliminary Controlled Trial
Authors: Arvin Ann M. , Feldman Sandor , Merigan Thomas C.
Published: June 2012

Eighteen patients who developed varicella while being treated for malignancy received human leukocyte interferon in a randomized double-blind placebo-controlled trial. Complications of varicella occurred in six of nine placebo recipients, but in only two of nine interferon recipients. Interferon was tolerated without significant side effects.
Plasmid-Determined Resistance to Hexachlorophene in
Pseudomonas aeruginosa
Authors: Sutton Lorraine , Jacoby George A.
Published: June 2012

Plasmid-containing strains of
Pseudomonas aeruginosa
were screened for resistance to disinfectants. Two plasmids, pMG1 and pMG2, were found to determine hexachlorophene resistance.
Cefuroxime, a Beta-Lactamase-Resistant Cephalosporin with a Broad Spectrum of Gram-Positive and -Negative Activity
Authors: Neu Harold C. , Fu Kwung P.
Published: June 2012

The in vitro activity of cefuroxime, a cephalosporin antibiotic, was investigated against 604 isolates and compared with the activity of other β-lactam compounds. Cefuroxime had activity comparable to that of other cephalosporins, including cefamandole and cefoxitin, against streptococcal and staphylococcal species; most streptococci were inhibited by 0.1 μg or less per ml, and staphylococci were inhibited by 1.6 μg or less per ml. Enterococci were relatively resistant. Cefuroxime inhibited β-lactamase-producing
Neisseria gonorrhoeae
and
Haemophilus influenzae
. Cefuroxime had excellent activity against members of the
Enterobacteriaceae;
83% of β-lactamase-producing
Escherichea coli
, 100% of
Salmonella
, 100% of
Klebsiella
, 90% of
Proteus mirabilis
, 95% of
Citrobacter
, 56% of
Enterobacter
, and 58% of
Shigella
were inhibited by 12.5 μg/ml. Cefuroxime had activity comparable to that of cefamandole and cefoxitin; it inhibited isolates of
E. coli
and
Klebsiella
resistant to cefamandole and inhibited
Enterobacter
and
Citrobacter
resistant to cefoxitin. Many isolates of
Serratia
, some indole-positive strains of
Proteus
, and
Bacteroides fragilis
were resistant to cefuroxime. Resistance of cefuroxime to hydrolysis by β-lactamases played a major role in its activity against both gram-positive and gram-negative organisms.
Tryptophan Uptake By
Mycobacterium tuberculosis
H
37
Rv: Effect of Rifampin and Ethambutol
Authors: Sundaram K. Soma , Venkitasubramanian T. A.
Published: June 2012

Uptake of radioactive tryptophan by
Mycobacterium tuberculosis
H
37
Rv grown in vitro and in vivo was investigated.

K
m

values indicated low affinity, and sodium azide inhibited uptake. Rifampin at the minimal inhibitory concentration had no effect, whereas ethambutol inhibited uptake only in the bacilli grown under in vitro conditions. The significance of these results is discussed.
In Vitro and In Vivo Studies of Ambruticin (W7783): New Class of Antifungal Antibiotics
Authors: Ringel Samuel M.
Published: June 2012

Ambruticin is a cyclopropyl-pyran acid, representing a new class of antibiotics. It has a relatively broad antifungal spectrum in vitro and is highly active against dimorphic as well as filamentous organisms. Of 24 strains of dermatophytic fungi tested, the majority were susceptible to ambruticin at 0.049 μg/ml or less. The minimal inhibitory concentration for the systemic fungi
Histoplasma capsulatum
and
Blastomyces dermatitidis
was 0.049 to 0.39 μg/ml. Ambruticin is fungicidal for metabolizing cells of
Microsporum fulvum
and does not cause cell leakage of 260-nm absorbing material. The antibiotic is effective orally as well as topically in guinea pigs experimentally infected with
Trichophyton mentagrophytes
. In mice, a single oral dose of 75 mg/kg produced peak serum levels of 45 μg/ml in 1 h with a serum half-life of 3.1 h. Excretion of the antibiotic is principally by the biliary route.