bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic Susceptibility of Black-Pigmented
Bacteroides
Isolates from the Human Oral Cavity
Authors: Laatsch Linda J. , Hohenfeldt Paul R. , Kos William L.
Published: June 2012

The minimal inhibitory concentrations of penicillin and six other antibiotics were determined for 66 oral black-pigmented
Bacteroides
isolates by using the National Committee for Clinical Laboratory Standards proposed standard agar dilution technique. These results plus iodometric determination of β-lactamase activity showed that oral isolates of black-pigmented
Bacteroides
are remaining relatively susceptible to commonly used antibiotics.
Conversion of amoscanate to a mutagenic metabolite in gnotobiotic mice implanted with Streptococcus equinus
Authors: Reddy B S , Batzinger R P , Molineaux C J , Bueding E
Published: June 2012

Recent in vitro studies indicate that intestinal bacteria convert amoscanate (4-nitro-4'-isothiocyanodiphenylamine), an antischistosomal drug, to a potent mutagen. The present study indicates that the implantation of germfree mice with Streptococcus equinus, isolated from the small intestine of conventional mice, restores the mutagenic activation of amoscanate in vivo.
In vitro activity of cefodizime (HR-221)
Authors: Ahonkhai V I , Cherubin C E , Shulman M A
Published: June 2012

The in vitro activity of cefodizime (HR-221), a new cephalosporin antibiotic, was compared with the activities of selected antimicrobial agents against a broad spectrum of aerobic bacteria. Cefodizime concentrations of 2 micrograms/ml inhibited about 90% of Enterobacteriaceae studied. Serratia marcescens required 8 micrograms/ml to inhibit 90% of strains. Among gram-positive cocci, 50% of strains were inhibited by 2 micrograms/ml of cefodizime (including methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis, and penicillin-resistant Streptococcus pneumoniae). Pseudomonas aeruginosa was less susceptible to cefodizime. Cefotaxime, an antibiotic closely related to cefodizime structurally, was about fourfold more active.
Antibacterial activities of SM-1652 compared with those of other broad-spectrum cephalosporins
Authors: Kato M , Inoue M , Mitsuhashi S
Published: June 2012

The in vitro and in vivo activities of Sm-1652 were compared with those of other cephalosporins. SM-1652 possessed a wide antibacterial spectrum which included activity against Pseudomonas aeruginosa. It also exhibited potent antibacterial activities against gram-positive cocci and clinical isolates of glucose nonfermentative bacteria. Most notably, its activity against glucose nonfermentative bacteria was the highest of all of the drugs tested. The bactericidal activity of SM-1652 was compared with that of cefoperazone. The difference between the minimum bactericidal concentration and the minimum inhibitory concentration of SM-1652 was actually smaller than that of cefoperazone for Escherichia coli and clinical isolates of indole-positive Proteus spp. SM-1652 was stable for most cephalosporinases but was hydrolyzed to some extent by penicillinases. The in vivo therapeutic effect of SM-1652 against infections in mice was better than those of cefazolin and cefoxitin. The in vivo antipseudomonal activity of SM-1652 was second to that of cefsulodin.
Transport of the lipophilic analog minocycline differs from that of tetracycline in susceptible and resistant Escherichia coli strains
Authors: McMurry L M , Cullinane J C , Levy S B
Published: June 2012

Plasmids which specify resistance to tetracycline offer much less resistance to its more lipophilic analog, minocycline. Resistance to minocycline varies for different plasmids. In the case of plasmid R222 (bearing the class B tetracycline resistance determinant on Tn10), minocycline resistance is comparatively high (10 microgram/ml, or 6% of the tetracycline resistance level). For plasmid pIP7 (bearing the class A determinant), minocycline resistance is only 1% of the tetracycline resistance level. To understand the basis for these differences, we compared the transport of the two tetracyclines by susceptible cells and by resistant cells. Uptake of minocycline by susceptible cells was 10 to 20 times more rapid than uptake of tetracycline and occurred largely via an energy-dependent route. This host-mediated energy-dependent uptake of both analogs was still present in tetracycline-resistant cells. In resistant cells, the same plasmid-mediated active efflux system previously described for tetracycline also exported minocycline. The 15-fold greater susceptibility of tetracycline-resistant R222-bearing cells to minocycline as compared with tetracycline could be explained at least in part by the more rapid influx of minocycline, which more easily overcame the efflux system. The particularly low minocycline resistance offered by pIP7 was due to a weak efflux for minocycline, 10-fold less effective than that mediated by R222. The rate-limiting step for uptake of both analogs appeared to be the outer membrane. That the lipophilic minocycline should cross this membrane more rapidly than tetracycline stands in contrast with other studies which show the outer membrane to be a barrier for entry of lipophilic substances.
Two-compartment comparison of gentamicin and tobramycin in normal volunteers
Authors: Adelman M , Evans E , Schentag J J
Published: June 2012

The objective of this study was to determine whether differences in tissue accumulation observed upon multiple dosing of aminoglycosides in hospitalized patients could be identified in appropriate single-dose studies in normal volunteers. Ten volunteers received single intravenous doses of 1.0 mg of gentamicin and tobramycin per kg of body weight in randomized crossover fashion. Multiple serum and urine samples were collected during the next 30 days. Serum aminoglycoside concentrations and urinary excretion rates were fitted to a two-compartment pharmacokinetic model, and parameters were derived. Tobramycin exhibited a higher clearance (P less than 0.08) and a lower volume of distribution at steady state (P less than 0.1), neither of which was significant. Tobramycin also showed a significantly lower predicted amount of drug in the body at steady state (P less than 0.05). These differences are consistent with observations made in patients receiving multiple doses. Single-dose studies appear to be capable of discriminating pharmacokinetic characteristics relevant to the comparative nephrotoxic potential of these two aminoglycosides.
Pharmacokinetic characteristics of intravenous ceftriaxone in normal adults
Authors: Pollock A A , Tee P E , Patel I H , Spicehandler J , Simberkoff M S , Rahal J J
Published: June 2012

The multiple-dose pharmacokinetics and tolerance of intravenous ceftriaxone were investigated in 44 adults with normal renal function. Doses of 0.5, 1.0, and 2.0 g every 12 h and 2 g every 24 h were administered intravenously at a constant rate over 30 min. Plasma and urine samples were collected after the first (day 1) and last (day 4) dose and assayed for ceftriaxone by high-pressure liquid chromatography. Considering all four doses, mean peak plasma concentrations ranged from 79 to 255 micrograms/ml on day 1 and from 101 to 280 micrograms/ml on day 4. Trough concentrations at 12 h on day 1 were 15 to 45 micrograms/ml and 20 to 59 micrograms/ml on day 4. After a dose regimen of 2 g every 24 h, trough levels were still in the clinically therapeutic range (13 to 15 microgram/ml). The mean beta-phase t1/2 was markedly long (6.3 to 6.9 h) and was independent of dose. The fraction of dose excreted unchanged in the urine (0.33 to 0.44) indicated a substantial nonrenal mechanism of elimination. The plasma clearance ranged between 1,002 and 1,449 ml/h, and renal clearance ranged from 353 to 529 ml/h. The apparent volume of distribution varied from 9.2 to 13.5 liters. The dose-related increases in calculated Vd and Clp could be attributed to concentration-dependent plasma protein binding because of a larger free fraction of drug at higher concentrations. The drug was well tolerated, and no significant clinical or laboratory abnormalities were noted.
Pharmacokinetics, protein binding, and extravascular distribution of ceftizoxime in normal subjects
Authors: Peterson L R , Gerding D N , Van Etta L L , Eckfeldt J H , Larson T A
Published: June 2012

Thirteen normal subjects were given 2, 3, or 4 g of ceftizoxime intravenously in a prospective single-blinded study. Serum and urine concentrations were measured for 48 h. The beta-phase serum half-life ranged from 1.4 to 1.7 h. Approximately 100% of the agent was recovered unchanged in the urine over 48 h. Six of 13 subjects reported subjective complaints consisting of mild dizziness and moderate headache, all of which were transient. One subject also had a minimally elevated serum glutamic oxalacetic transaminase level 1 day after drug administration. Based on serum pharmacokinetics and serum protein binding determined in this investigation, unbound ceftizoxime appeared to distribute with the total body water.
Monitoring of plasmid-encoded, trimethoprim-resistant dihydrofolate reductase genes: detection of a new resistant enzyme
Authors: Fling M E , Walton L , Elwell L P
Published: June 2012

Using-gene-specific radiolabeled probe DNAs, we analyzed 42 clinical bacterial isolates with high-level trimethoprim (Tp) resistance for the presence of a type I or a type II plasmid-specified dihydrofolate reductase (DHFR) gene. Plasmid DNA from 17 strains harbored a type I DHFR, whereas 11 isolates contained plasmids that harbored a type II DHFR structural gene. The plasmid DNAs from five strains appeared to hybridize with both type I and type II DHFR probe DNAs. In addition, eight isolates had type I resistance determinants integrated into the chromosomes, presumably on transposon 7 (Tn7). Among the strains analyzed in this survey, none of the chromosomally located, Tp-insensitive reductases were of the type II class. Both the plasmid and chromosomal DNAs of one isolate showed no homology with either the type I or type II DHFR probe DNA. The plasmid harbored by this strain encoded a "new" Tp-resistant enzyme that differed significantly, both in molecular weight and with respect to trimethoprim and methotrexate inhibition kinetics, from the previously characterized plasmid-associated dihydrofolate reductases.
Activity of pirlimycin (U57930E) against strains of the Bacteroides fragilis group
Authors: Garcia-Rodriguez J A , Garcia-Sanchez J E , Prieto J , Sanchez de S Lorenzo A
Published: June 2012

The activities of pirlimycin (U57930E), lincomycin, clindamycin, erythromycin, josamycin, oleandomycin, and spiramycin were compared against strains of the Bacteroides fragilis group. Pirlimycin was the most active; the 90% minimal inhibitory concentration was 1 microgram/ml, and the activity range was 0.125 to 4 micrograms/ml. This drug was fourfold more active than any of the other drugs, including clindamycin. The minimal bactericidal concentration (range, 0.5 to 16 micrograms/ml) shows that pirlimycin behaves as a bacteriostatic antibiotic.
Susceptibility of clinical isolates of Staphylococcus saprophyticus to fifteen commonly used antimicrobial agents
Authors: Nicolle L E , Harding G K
Published: June 2012

Susceptibility of 34 recent clinical isolates of Staphylococcus saprophyticus to 16 commonly used antimicrobial agents was studied. Strains were uniformly resistant to nalidixic acid but tended to be sensitive to other agents, with occasional resistance noted to penicillin (3%), tetracycline (6%), sulfamethoxazole (6%), and erythromycin (15%).
Evaluation of the Cathra inoculating device for susceptibility testing of methicillin-susceptible and methicillin-resistant Staphylococcus aureus strains
Authors: Boyce J M , Bonner M C , Lockwood W R
Published: June 2012

We compared the antimicrobial susceptibility results obtained with the Cathra replicator and reference methods when Staphylococcus aureus strains were tested by using agar dilution techniques. The Cathra replicator and the 0.001-ml calibrated loop gave results that fell within +/- 1 log2 dilution for greater than or equal to 95% of isolates when methicillin and cefamandole were tested.
Synergism Between Vancomycin and Gentamicin or Tobramycin for Methicillin-Susceptible and Methicillin-Resistant
Staphylococcus aureus
Strains
Authors: Watanakunakorn Chatrchai , Tisone Joann C.
Published: June 2012

By the time-kill curve method, the combinations of vancomycin-gentamicin and vancomycin-tobramycin were shown to be synergistic against a majority of methicillin-susceptible and -resistant strains of
Staphylococcus aureus
.
Nonenzymatic chloramphenicol resistance determinants specified by plasmids R26 and R55-1 in Escherichia coli K-12 do not confer high-level resistance to fluorinated analogs
Authors: Dorman C J , Foster T J
Published: June 2012

Plasmids R26 (Inc P) and R55-1 (Inc C) specify inducible nonenzymatic resistance to chloramphenicol. Escherichia coli K-12 strains harboring these plasmids encoded low-level resistance to thiamphenicol analogs Sch 25298 and Sch 25393 but failed to specify resistance to the fluorinated chloramphenicol analog Sch 24893. The analogs were efficient inducers of high-level chloramphenicol resistance.
Antagonism Between Nafcillin or Oxacillin and Rifampin Against
Staphylococcus aureus
Authors: Watanakunakorn Chatrchai , Tisone Joann C.
Published: June 2012

By the time-kill method, the combinations of nafcillin plus rifampin and oxacillin plus rifampin were antagonistic against 20 strains of
Staphylococcus aureus
. No synergism was demonstrated.
Topical enviroxime against rhinovirus infection
Authors: Levandowski R A , Pachucki C T , Rubenis M , Jackson G G
Published: June 2012

Enviroxime, an inhibitor of rhinovirus replication, was studied in a double-blind, placebo-controlled trial with 99 volunteers. The efficacy of a nasal-spray formulation of enviroxime was tested as pretreatment or as postchallenge treatment for rhinovirus type 4 infection. In the regimens used, drug administration neither prevented infection nor reduced the frequency of specific colds. The mean concentration of enviroxime in nasal washes (12 h after a dose) differentiated two groups of responders. Those in whom the drug concentration exceeded 100 ng/ml had some benefits, although these were statistically insignificant.
Serum assays of netilmicin by enzyme multiplied immunoassay technique and bioassay: a comparative study
Authors: Jansson L , Henning C
Published: June 2012

Serum concentration determinations of netilmicin obtained with bioassay and the enzyme multiplied immunoassay technique were compared. There was no statistically significant difference between the precision of the two techniques (P greater than 0.05). When clinical serum was used, a systematic error was demonstrated between the enzyme multiplied immunoassay technique and bioassay.
Pharmacokinetics of Cefadroxil and Cefaclor During an Eight-Day Dosage Period
Authors: Hampel Barbara , Lode Hartmut , Wagner Jutta , Koeppe Peter
Published: June 2012

The concentrations of cefadroxil and cefaclor in serum were studied in eight healthy volunteers receiving 1,000 mg of both substances three times per day for 8 days. Intraindividual comparisons showed an increase in peak serum levels of cefadroxil from days 1 to 8 in seven of eight volunteers. Cefaclor peak concentrations did not rise during the 8 days.
Homogeneous enzyme immunoassay for netilmicin
Authors: Wenk M , Hemmann R , Follath F
Published: June 2012

A newly developed homogeneous enzyme immunoassay for the determination of netilmicin in serum was evaluated and compared with a radioenzymatic assay. A total of 102 serum samples from patients treated with netilmicin were measured by both methods. This comparison showed an excellent correlation (r = 0.993). The enzyme immunoassay has proved to be precise, accurate, and specific. Because of its rapidity and the ease of performance, this method is a useful alternative to current assays for monitoring serum netilmicin concentrations.
Iron requirement in the bactericidal mechanism of streptonigrin
Authors: Yeowell H N , White J R
Published: June 2012

Mutants of Escherichia coli K-12 that are unable to make use of the enterochelin transport system were used to confirm that streptonigrin requires iron for its bactericidal action. Correlation of viability studies and 55Fe3+ uptake experiments showed that killing by streptonigrin increased with an increase in 55Fe3+ uptake by the cells. Streptonigrin did not kill iron-starved mutants that were unable to import iron. The level of iron uptake by these mutants was manipulated by agents such as (i) the enterochelin biosynthetic precursors 2,3-dihydroxybenzoic acid (2 x 10(-5) M) and shikimic acid (2 x 10(-4) M), (ii) citrate (10(-2) M), which promotes iron uptake by an independent pathway, and (iii) the chelating agents desferrioxamine (2 x 10(-4) M) and orthophenanthroline (10(-4) M). Addition of the precursors shikimate and dihydroxybenzoate to strain AB2847 (aroB) and dihydroxybenzoate to strain AN193 (entA), allowing these strains to make enterochelin, resulted in an increase in Fe3+ uptake and a corresponding sharp increase in killing by streptonigrin. Addition of enterochelin itself (10(-6) M) caused an even more pronounced effect. Studies on the effect of citrate in strain AN102 (fep) showed that this mutant was not killed by streptonigrin (4 x 10(-5) M), even in the presence of citrate; however, overnight growth in citrate induced Fe3+ uptake by means of the ferric citrate transport system and resulted in killing by streptonigrin. These studies showed a clear correlation between the change in levels of intracellular iron and the bactericidal effectiveness of streptonigrin.
In vitro assessment of 2-acetylpyridine thiosemicarbazones against chloroquine-resistant Plasmodium falciparum
Authors: Lambros C , Childs G E , Notsch J D , Scovill J P , Klayman D L , Davidson D E
Published: June 2012

A series of 2-acylpyridine thiosemicarbazones was evaluated in vitro against a chloroquine-resistant Plasmodium falciparum strain. Antimalarial activity was assessed by the inhibition of uptake of [G-3H]hypoxanthine by the parasites. Among the mono- and disubstituted derivatives tested, 13 of 17 had 50% inhibitory doses of less than 10 ng/ml. Increasing the size of the ring at N4 from four to five, six, and seven members produced concomitant decreases in activity. Similarly, increasing the size of the aliphatic substituent on the azomethine carbon reduced activity. Selected compounds were also tested against a chloroquine-susceptible strain. The results suggested that the activities of these agents were not modified significantly by resistance to chloroquine. In general, in vitro activities correlate poorly with the in vivo activities in mice infected with Plasmodium berghei.
Effects of pH on the Activity of Ketoconazole Against
Candida albicans
Authors: Minagawa Harushige , Kitaura Kozo , Nakamizo Nobuhiro
Published: June 2012

The activity of ketoconazole against
Candida albicans
in Sabouraud glucose medium was markedly influenced by pH. Minimum inhibitory concentrations of this imidazole against both a standard strain and clinical isolates ranged from 40 μg/ml at pH 3 to 0.02 μg/ml at pH 7, a greater than 1,000-fold difference.
Differences Among
Nocardia
spp. in Susceptibility to Aminoglycosides and β-Lactam Antibiotics and Their Potential Use in Taxonomy
Authors: Wallace Richard J. , Wiss Karen , Curvey Ron , Vance Paula H. , Steadham Joe
Published: June 2012

Using disk diffusion and agar dilution methods, 109 clinical isolates of
Nocardia
were tested against 10 antimicrobial agents. A species difference in susceptibility was noted for cefamandole, carbenicillin, gentamicin, and kanamycin. These differences in susceptibility may be of use taxonomically as well as having some potential use clinically.
In vitro susceptibility of spiroplasmas to heavy-metal salts
Authors: Whitmore S C , Rissler J F , Davis R E
Published: June 2012

The susceptibility of six spiroplasma strains to heavy-metal salt was characterized in terms of minimal inhibitory concentrations and minimal biocidal concentrations in broth tube dilution tests. The strains were most susceptible to mercuric chloride and silver nitrate; less susceptible to copper sulfate, cobalt chloride, lead nitrate, and cadmium sulfate; and least susceptible to nickel chloride and zinc sulfate. Spiroplasma citri strains Maroc R8A2 and C189 were the most susceptible to five of eight heavy-metal salts, and honeybee spiroplasma strain AS576 and Spiroplasma floricola strain 23-6 were generally the least susceptible. The difference between the minimal biocidal concentrations and the minimal inhibitory concentrations was greater for certain heavy-metal salts than for others.
Pharmacokinetics of cefotetan in normal subjects and patients with impaired renal function
Authors: Ohkawa M , Hirano S , Tokunaga S , Motoi I , Shoda R , Ikeda A , Sugata T , Sawaki M , Shimamura M , Okasho A , Kuroda K
Published: June 2012

The elimination kinetics of cefotetan (YM09330), a new parenteral semisynthetic cephamycin derivative, were studied in eight healthy volunteers and 41 patients with renal insufficiency after the administration of a single 500-mg dose intravenously. Concentrations of cefotetan in serum and urine were determined by both bioassay and high-pressure liquid chromatography. The pharmacokinetic parameters for cefotetan were calculated on the basis of a two-compartment open model. Serum concentrations of cefotetan immediately after administration were approximately 180 micrograms/ml in all subjects regardless of function; however, serum concentrations during the beta-phase increased directly with the degree of renal impairment. The mean serum half-life during the beta-phase was 3.0 h in normal subjects as compared with 13.1 h in hemodialysis patients. There was a linear correlation (P less than 0.0001) between the elimination rate constant of cefotetan and creatinine clearance. The mean cumulative urinary recovery of cefotetan in the 24-h urine was 83.3% of the administered dose in normal subjects and decreased with reduced renal function.
Comparison Study of the Kinetics of Ceftizoxime Penetration into Extravascular Spaces with Known Surface Area/Volume Ratio In Vitro and In Vivo in Rabbits
Authors: Van Etta Linda L. , Fasching Claudine E. , Peterson Lance R. , Gerding Dale N.
Published: June 2012

The extravascular kinetics of ceftizoxime were studied both in an in vitro kinetic model and in an in vivo rabbit model. Visking tubing chambers were used in both models to provide extravascular spaces with large or small volumes and surface areas, but identical surface area/volume ratios. Four rabbits, each implanted with two large Visking chambers and four small chambers, received 50 mg of ceftizoxime per kg intramuscularly every 3 h for eight doses. In the in vitro model, 80 mg of ceftizoxime was infused over 30 min every 3 h for eight doses. Intravascular and extravascular spaces were sampled in both models after the eighth dose. Ceftizoxime had similar intravascular kinetics in both models, i.e., the peak levels, the peak-to-trough fluctuations, and the half-life were comparable. The area under the curve (AUC) for the extravascular spaces was also similar in the two models. Large and small chambers having identical surface area/volume ratios demonstrated identical kinetics. The extravascular Visking chamber spaces achieved equilibrium with the intravascular spaces in both models, i.e., the AUC for the extravascular spaces was the same (
P
> 0.2) as that for the serum (rabbit model) or the test chamber (in vitro model). This study illustrates (i) that our modified in vitro model is a potentially valid model for studying extravascular kinetics; (ii) that extravascular spaces with identical surface area/volume ratios show similar penetration kinetics with a freely diffusible drug, such as ceftizoxime, despite differences in size; and (iii) that the Visking chamber extravascular-space model permits the free diffusion of the antimicrobial agent and reaches equilibrium (equivalent AUC) with the intravascular space.
Mechanisms of action of 5-fluorocytosine
Authors: Waldorf A R , Polak A
Published: June 2012

5-Fluorouracil and 5-fluorodeoxyuridine monophosphate levels were estimated in 75 isolates of Candida albicans to determine whether 5-fluorocytosine susceptibility could be ideally correlated with the intrafungal formation of both 5-fluorodeoxyuridine monophosphate and 5-fluorouridine triphosphate or a reciprocal formation of the two metabolites to prove the mechanism of 5-fluorocytosine activity. Using the results of four in vitro susceptibility tests, we separated isolates of C. albicans into susceptibility groups. For most strains, there was a positive correlation between the degree of 5-fluorocytosine susceptibility and the inhibition of biosynthesis of both RNA and DNA, incorporation of 5-fluorouracil into RNA, inhibition of ribosomal protein synthesis, and levels of 5-fluorodeoxyuridine monophosphate. However, in some strains with a similar degree of 5-fluorocytosine resistance, either reduced incorporation of 5-fluorouracil or reduced 5-fluorodeoxyuridine monophosphate levels occurred, suggesting that these two mechanisms are not necessarily linked to each other and that both may be responsible for 5-fluorocytosine activity.
Binding of monobactams to penicillin-binding proteins of Escherichia coli and Staphylococcus aureus: relation to antibacterial activity
Authors: Georgopapadakou N H , Smith S A , Cimarusti C M , Sykes R B
Published: June 2012

A series of novel monocyclic beta-lactam antibiotics having side chains related to penicillin, piperacillin, azlocillin, and cefotaxime were examined with respect to binding to essential penicillin-binding proteins (PBPs) in Escherichia coli and Staphylococcus aureus. In the penicillin series, there was poor binding to all essential PBPs of E. coli (greater than 100 micrograms/ml) but good binding to PBPs 1, 2, and 3 of S. aureus (approximately 1 microgram/ml). In the piperacillin and azlocillin series, there was good binding to PBP 3 of E. coli (0.1 microgram/ml) and PBPs 1, 2, and 3 of S. aureus (approximately 1 microgram/ml). In the cefotaxime series, there was generally good binding to PBP 3 of E. coli (0.1 micrograms/ml) but poor binding to PBPs 1, 2, and 3 of S. aureus (greater than or equal to 100 micrograms/ml). With a few exceptions in the cefotaxime series, antibacterial activity paralleled essential PBP binding. Binding studies with radioactively labeled compounds revealed no additional essential monobactam-binding proteins in the two organisms. The studies suggest that monobactams are intrinsically active against both gram-positive and gram-negative bacteria; the activity spectrum of a given monobactam is determined by the binding to essential PBPs, which in turn is determined by the nature of the substituents on the beta-lactam nucleus.
Susceptibility of Bordetella species to growth inhibition and killing by chlorpromazine
Authors: Hewlett E L , Myers G A , Pearson R D
Published: June 2012

Chlorpromazine, the prototype phenothiazine tranquilizer, inhibited the growth and killed organisms of the genus Bordetella. There were striking differences, however, among the three Bordetella species. Bordetella pertussis was most susceptible, with some inhibition of growth at greater than or equal to 4 micrograms/ml and killing at 16 micrograms of chlorpromazine per ml. Bordetella parapertussis and Bordetella bronchiseptica were less susceptible, with killing at 32 and 256 micrograms/ml, respectively. Although the phenothiazines were inhibitory for Bordetella extracytoplasmic adenylate cyclase, the lethal effect occurred at a lower concentration and did not appear to involve modification of the enzyme activity. Exposure of B. pertussis to combinations of chlorpromazine and erythromycin resulted in impaired growth at concentrations lower than that of either drug alone, but there was no evidence that the two drugs interacted either synergistically or antagonistically.
Ketoconazole inhibition of testicular secretion of testosterone and displacement of steroid hormones from serum transport proteins
Authors: Grosso D S , Boyden T W , Pamenter R W , Johnson D G , Stevens D A , Galgiani J N
Published: June 2012

In vivo perfusion of canine testes with ketoconazole inhibited the stimulation of testosterone production by human chorionic gonadotropin in a dose-dependent manner. Ketoconazole also selectively displaced steroids from serum-binding globulins. Dihydrotestosterone and estradiol binding to sex hormone-binding globulin were inhibited by ketoconazole. Cortisol binding to corticosteroid-binding globulin was unaffected. The concentrations of ketoconazole that inhibited human chorionic gonadotropin stimulation of testicular androgen production and displaced sex steroids from sex hormone-binding globulin were in the range of blood levels found in patients on higher therapeutic dosage regimens. Suppression of testicular testosterone synthesis and displacement of estrogens from sex hormone-binding globulin may decrease the androgen/estrogen ratio of the blood and contribute to the development of gynecomastia that has been reported in some ketoconazole-treated patients.
Comparative study of ceftriaxone and aqueous procaine penicillin G in the treatment of uncomplicated gonorrhea in women
Authors: Judson F N , Ehret J M , Root C J
Published: June 2012

Uncomplicated gonorrhea of 122 mucosal sites in 51 women was successfully treated with either a single intramuscular dose of 250 mg of ceftriaxone (23 patients) or two intramuscular doses of 4.8 X 10(6) U of aqueous procaine penicillin G (28 patients). Women treated with ceftriaxone had 22 cervical, 12 urethral, 10 anal canal, and 5 pharyngeal infections. All 122 pretreatment isolates were inhibited by 0.0125 microgram or less of ceftriaxone per ml. The minimal concentration needed to inhibit 90% of isolates was 0.006 microgram/ml for ceftriaxone and 0.2 microgram/ml for penicillin G. Ceftriaxone was very well tolerated and caused no toxicity.
Tentative interpretive standards for disk diffusion susceptibility testing with norfloxacin (MK-0366, AM-715)
Authors: Shungu D L , Weinberg E , Gadebusch H H
Published: June 2012

Norfloxacin is a new orally absorbed quinoline derivative structurally related to nalidixic acid but showing an expanded antibacterial spectrum which includes Enterobacteriaceae, Pseudomonas aeruginosa, Streptococcus faecalis, and staphylococci, among other susceptible bacterial species. The application of the regression line and error rate-bounded methods of analysis to the minimal inhibitory concentration and zone size data collected on 413 clinical isolates favored the selection of a 10-micrograms disk content and the adoption of the following interpretive zone size breakpoints for antimicrobial susceptibility testing with norfloxacin: greater than or equal to 17 mm for susceptible, 13 to 16 mm for intermediate, and less than or equal to 12 mm for resistant categories. It is proposed that isolates with minimal inhibitory concentrations of less than or equal to 16 and greater than or equal to 32 micrograms/ml be considered susceptible and resistant to norfloxacin, respectively. Differences in the antibiotic disk contents and in vitro antibacterial spectra and pharmacokinetic properties, together with the much lower rates of cross-resistance reported between norfloxacin and related drugs, strongly argue against the use of the "class disk" concept in this instance and suggest that the 10-micrograms norfloxacin susceptibility disk should be tested separately.
Peroxidase-Thiocyanate-Peroxide Antibacterial System Does Not Damage DNA
Authors: White William E. , Pruitt Kenneth M. , Mansson-Rahemtulla Britta
Published: June 2012

The hypothiocyanite ion (OSCN
-
) is a normal component of human saliva. It is a highly reactive oxidizing agent, and at concentrations above the values normally found in human saliva, it inhibits the growth and metabolism of oral bacteria. This finding has led to the suggestion that antibacterial properties of human saliva might be enhanced in vivo by appropriate supplements which elevate OSCN
-
concentrations. Since DNA is sensitive to oxidizing agents (hydrogen peroxide attacks nucleosides), high concentrations of OSCN
-
in human saliva might damage DNA and produce deleterious effects on the oral mucosa. In the present study, the effect of high OSCN
-
concentrations on several mutagen-sensitive
Salmonella typhimurium
strains was determined. These strains are used to detect base-pair substitutions and frameshift mutations. We also studied the effects of OSCN
-
on a
Saccharomyces cerevisiae
(yeast) strain commonly employed as a test cell for evaluating the potential of a compound to produce gene conversion, mitotic crossing-over, or reverse mutation. By recording the UV spectra of mixtures of calf thymus DNA and OSCN
-
, we explored the possible in vitro reactions of this oxidizing agent with eucaryotic genetic material. Our results show that, at concentrations above 10 μM, OSCN
-
is toxic for the tested
Salmonella typhimurium
strains. The mutant strains with defects in cell wall lipopolysaccharides are killed more readily by OSCN
-
than is the strain lacking these defects. However, OSCN
-
was not mutagenic for any of the tested strains.
Saccharomyces cerevisiae
was not affected by OSCN
-
even at concentrations above 800 μM. Calf thymus DNA was not oxidized by OSCN
-
. We conclude that the elevated concentrations of OSCN
-
required to produce antibacterial effects in the human mouth pose no threat to the genetic material of host tissues.
Inhibition of melanogenesis in B16-F1 melanoma cells after exposure to diflubenzuron
Authors: Norman J O , Meola S M
Published: June 2012

The insect growth regulator diflubenzuron was found to be a potent inhibitor of melanosome synthesis and release in mouse melanoma cell cultures, and after three to five successive passages of melanoma cells in growth medium containing this compound, these cells were unable to produce monolayers in untreated medium and were incapable of inducing tumor formation in mice. This is the first time that an insect growth regulator has been shown to have a deleterious effect on malignant cells of animals.
Isolation of Plasmids Encoding Tetracycline Resistance from
Campylobacter jejuni
Strains Isolated from Simians
Authors: Tenover F. C. , Bronsdon M. A. , Gordon K. P. , Plorde J. J.
Published: June 2012

Fifteen isolates of tetracycline-resistant
Campylobacter jejuni
were recovered from stool samples of cynomologous monkeys (
Macaca fascicularis
) housed at the University of Washington Primate Research Center, Seattle. Resistance was associated with carriage of a 38-megadalton plasmid which was transmissible to other strains of
C. jejuni
but not to
Escherichia coli
. Seven isolates also contained a 2.6-megadalton plasmid which was phenotypically cryptic.
Effect of Acyclovir on Viral Protein Synthesis in Cells Infected with Herpes Simplex Virus Type 1
Authors: Furman Phillip A. , McGuirt Paul V.
Published: June 2012

The effect of the antiviral agent 9-(2-hydroxyethoxymethyl)guanine (acyclovir) on herpes simplex virus type 1 protein synthesis during virus replication was examined. Treatment of infected cells with acyclovir markedly affected the amounts of the four major glycosylated and certain non-glycosylated viral polypeptides synthesized; other viral polypeptides were made in normal amounts. The reduced amount of late protein synthesis was most likely due to the inhibition of progeny viral DNA synthesis by acyclovir.
Gentamicin persistence in rat endolymph and perilymph after a two-day constant infusion
Authors: Tran Ba Huy P , Meulemans A , Wassef M , Manuel C , Sterkers O , Amiel C
Published: June 2012

The kinetics of gentamicin in the inner ear fluids of rats were studied up to 15 days after cessation of a 2-day constant infusion of 10 micrograms/min. In endolymph, the concentration of gentamicin persisted at about 1 microgram/ml for up to 15 days, precluding the determination of the half-life of the drug in this fluid. In perilymph, gentamicin cleared more slowly than after a shorter period of infusion. These results suggest that the tissues of the inner ear could bind the aminoglycoside and then slowly release it into the surrounding fluids.
Effects of moxalactam and cefuroxime on mitogen-stimulated human mononuclear leukocytes
Authors: Manzella J P , Clark J K
Published: June 2012

The effect of moxalactam and cefuroxime on mitogen-stimulated human peripheral blood mononuclear leukocytes was studied. Mononuclear leukocytes, mitogen, and antibiotic were added to microtiter wells. Cells were cultured for 3 days, pulsed with tritiated thymidine, and then counted. Compared with control cell cultures, treated cultures showed phytohemagglutinin responsiveness to be depressed by the addition of moxalactam at concentrations of 25 to 200 micrograms/ml (P less than 0.001) and by cefuroxime at concentrations of 50 to 200 micrograms/ml (P less than 0.02 to P less than 0.01). The depressive effect on blastogenesis was less marked when concanavalin A was used. Unstimulated lymphocyte transformation responses were also depressed by both antibiotics at all concentrations (P less than 0.05). Preincubation of mononuclear leukocytes with antibiotic for 2 h, followed by washing and culturing in an antibiotic-free medium, did not depress transformation response. When antibiotic was added 24 h after mitogen, depression of response was insignificant. The data from this study suggest that two new beta-lactam antibiotics, at concentrations achievable in serum when used therapeutically, may have immunosuppressant effects. It remains to be established whether these effects are clinically important.
In vitro antiplaque activity of octenidine dihydrochloride (WIN 41464-2) against preformed plaques of selected oral plaque-forming microorganisms
Authors: Slee A M , O'Connor J R
Published: June 2012

The antibacterial activity of octenidine dihydrochloride (WIN 41464-2) against intact preformed in vitro plaques of four indigenous oral plaque-forming microorganisms, Streptococcus mutans, Streptococcus sanguis, Actinomyces viscosus, and Actinomyces naeslundii, was studied. Both absolute (plaque bactericidal index) and relative (chlorhexidine coefficient) indices of antiplaque efficacy were established. Octenidine dihydrochloride compared favorably with chlorhexidine digluconate with respect to overall antiplaque potency in this in vitro plaque bactericidal model. These data indicate that prudent selection of treatment concentration and duration and frequency of exposure should provide an effective means to aid in controlling dental caries and Actinomyces-associated disease in vivo.
Serotype distribution of penicillin-resistant pneumococci and their susceptibilities to seven antimicrobial agents
Authors: Michel J , Dickman D , Greenberg Z , Bergner-Rabinowitz S
Published: June 2012

A total of 229 clinical isolates of Streptococcus pneumoniae recovered from 225 patients were serotyped and tested for susceptibility to penicillin G, ampicillin, mezlocillin, cefazolin, erythromycin, clindamycin, chloramphenicol, and sulfamethoxazole-trimethoprim. Of all the isolates, 48 (21.0%) showed intermediate resistance and 17 (7.4%) showed resistance to penicillin G. Penicillin-resistant strains had higher minimal inhibitory concentrations of ampicillin, mezlocillin, and cefazolin than did penicillin-susceptible strains. Resistance to erythromycin and clindamycin was rare (1.3 and 0.9%, respectively). Of the isolates, 8.7% were resistant to sulfamethoxazole-trimethoprim, and all were susceptible to chloramphenicol. Penicillin resistance was associated with 13 serotypes. Serotypes 14, 19F, 19A, and 23F were both highly prevalent and frequently penicillin resistant.
Possible molecular basis for antiviral activity of certain 5-substituted deoxyuridines
Authors: Sim I S , Goodchild J , Meredith D M , Porter R A , Raper R H , Viney J , Wadsworth H J
Published: June 2012

The antiviral activity of five structurally related pyrimidine nucleosides, E-5-propenyl-2'-deoxyuridine, 5-allyl-2'-deoxyuridine, E-5-(1-butenyl)-2'-deoxyuridine, 5-(2-butenyl)-2'-deoxyuridine, and 5-butyl-2'-deoxyuridine, in cell culture against herpes simplex virus type 1 was examined. Analogs in which the C-C double bond of the 5-substituent was in conjugation with the pyrimidine ring were more potent antiviral drugs than were the corresponding nonconjugated and alkyl-substituted analogs. Differences in antiviral activity similar to those observed in cell culture occurred in virus-infected mice. The molecular basis for the greater antiviral activity of the conjugated isomers was investigated. It was observed that the conjugated isomer E-5-propenyl-2'-deoxyuridine had a greater affinity for virus thymidine kinase and, as the 5'-triphosphate, for virus DNA polymerase than did the nonconjugated isomer 5-allyl-2'-deoxyuridine. The results are discussed in relation to other data in the literature.
Comparative pharmacokinetics of cefoperazone, cefotaxime, and moxalactam
Authors: Kemmerich B , Lode H , Belmega G , Jendroschek T , Borner K , Koeppe P
Published: June 2012

The pharmacokinetics of cefoperazone, cefotaxime, and moxalactam were compared in a cross-over randomized study in 10 healthy volunteers. Each subject received 1.0 g of the three drugs by bolus intravenous injection over 3 min. Serum and urine concentrations were assayed by a microbiological method and in addition by high-pressure liquid chromatography (HPLC) for cefotaxime in five subjects. Maximal concentrations in serum 5 min after the injection were 163 +/- 40.3 mg/liter for cefoperazone, 86.1 +/- 19.0 mg/liter for cefotaxime, and 95.5 +/- 21.1 mg/liter for moxalactam. After 12 h, 1.2 +/- 1.4 mg of cefoperazone per liter and 1.8 +/- 0.9 mg of moxalactam per liter could still be measured. Eight hours after the administration of cefotaxime, serum concentrations were below the detection limit of 0.3 mg/liter in most subjects. By HPLC analysis, the mean maximal concentration of desacetyl cefotaxime was 16.6 +/- 10.5 mg/liter 5 min after application; the metabolite exceeded the serum concentration of the parent compound after 1 to 2 h. Relevant pharmacokinetic parameters were calculated, using two- and three-compartment models. The terminal half-life was 144.1 +/- 37.3 min for cefoperazone, 76.1 +/- 32.0 min for cefotaxime, and 272.4 +/- 114.1 min for moxalactam. The apparent volume of distribution corresponded to the extracellular volume. Only 25.1 +/- 8% of cefoperazone could be detected in urine compared with 53.3 +/- 8.1% of cefotaxime and 61.0 +/- 9.2% of moxalactam in 24 h. A total of 89.6 +/- 11.4% of the cefotaxime dose could be recovered by HPLC in urine, 60.6 +/- 7.7% as cefotaxime and 29.1 +/- 7.0% as desacetyl cefotaxime.
Comparative in vitro study of teichomycin A2
Authors: Fainstein V , LeBlanc B , Bodey G P
Published: June 2012

Teichomycin A2 was evaluated in vitro against clinical isolates, and its activity was compared with that of other antibiotics. This compound was very active against all organisms tested; its activity was comparable to that of vancomycin, and it was superior to several other antibiotics when tested against gram-positive cocci. Because of its in vitro activity, it deserves clinical evaluation.
R Plasmids in
Corynebacterium xerosis
Strains
Authors: Kono Megumi , Sasatsu Masanori , Aoki Takashi
Published: June 2012

Plasmids coding for resistance to chloramphenicol, erythromycin, kanamycin, streptomycin, and tetracycline have been found in strains of
Corynebacterium xerosis
isolated from patients with otitis media.
Membrane potential in anaerobically growing Staphylococcus aureus and its relationship to gentamicin uptake
Authors: Mates S M , Patel L , Kaback H R , Miller M H
Published: June 2012

The electrical potential (delta psi) across the cytoplasmic membranes of Staphylococcus aureus cells growing under aerobic and anaerobic conditions was determined by measuring the equilibrium distribution of [3H]tetraphenyl phosphonium. In conjunction, gentamicin uptake and killing were studied in the same cells under identical conditions. Under aerobic conditions, delta psi was -169 mV, gentamicin uptake was readily demonstrable, and the number of viable cells decreased by almost four orders of magnitude in the presence of antibiotic. In contrast, delta psi was -142 mV anaerobically, gentamicin uptake was essentially nonexistent, and the aminoglycoside had no effect on viability. Remarkably, when the ionophore nigericin was added under anaerobic conditions, delta psi increased to the level observed aerobically, gentamicin uptake tripled to about 18% of the aerobic level, and viability decreased by one order of magnitude. The results are consistent with other observations (Mates et al., Proc. Natl. Acad. Sci. U.S.A. 79:6693-6697, 1982), indicating that the relationship between delta psi and gentamicin uptake is gated, and suggest that diminution of delta psi may be an important factor in aminoglycoside resistance under anaerobic conditions.
Relationship between structure and antiplaque and antimicrobial activities for a series of bispyridines
Authors: Slee A M , O'Connor J R , Bailey D M
Published: June 2012

A series of bispyridines were examined for their bactericidal activities against in vitro, preformed, pure-culture plaques of selected oral plaque-forming bacteria. The antimicrobial activities of these agents were examined in relation to their molecular configurations. These studies demonstrated that the length of the interpyridine polymethylene group bridge and the length of the alkyl side chain were important determinants of antiplaque and antimicrobial efficacy. The most potent compounds of the bispyridine series were studied to determine the minimal conditions (concentration, duration, and frequency) of treatment required for likely clinical efficacy.
Sulfur metabolism in the biosynthesis of monobactams
Authors: O'Sullivan J , Souser M L , Kao C C , Aklonis C A
Published: June 2012

We studied the biosynthesis of monobactams with respect to sulfur metabolism in Chromobacterium violaceum, Acetobacter sp., and Agrobacterium radiobacter. All three organisms used inorganic sulfur for monobactam production. When sulfur-containing amino acids were assayed as a source of sulfur for monobactam production, C. violaceum used cystine but not cysteine or methionine, Acetobacter sp. used all three compounds, and A. radiobacter used none. 35S from cysteine, methionine, and sodium sulfate was incorporated into monobactam by Acetobacter sp. Cell-free extracts of all three organisms were shown to possess cysteine desulfhydrase activity. In Acetobacter sp., this activity was constitutive, required pyridoxal phosphate, and had a pH optimum of 9.5. Extensive loss of 3H from L-[3-3H]cysteine was seen upon desulfhydration; no evidence of serine formation was found. Active sulfate was formed in cell-free extracts of A. radiobacter, and, since inorganic sulfur was used by all three organisms, it is likely that the sulfamate group of monobactams is produced via active sulfate.
Methicillin-resistant septal peptidoglycan synthesis in a methicillin-resistant Staphylococcus aureus strain
Authors: Wilkinson B J , Nadakavukaren M J
Published: June 2012

In a methicillin-resistant Staphylococcus aureus strain, electron micrographs showed that cell wall septa continued to be formed in the presence of methicillin, although they became distorted and enlarged. The results indicated that peripheral cell wall synthesis was inhibited. It is concluded that a methicillin-resistant mode of septal peptidoglycan synthesis is an important determinant of methicillin resistance.
Importance of minimizing carry-over effect at subculture in the detection of penicillin-tolerant viridans group streptococci
Authors: Dankert J , Holloway Y , Joldersma W , Hess J
Published: June 2012

Penicillin susceptibility determinations made for 14 strains of Streptococcus mitior by two different broth dilution tests revealed small numbers of tolerant strains regardless of the volumes (0.01 and 0.1 ml) of subcultured broth. The addition of penicillinase to the subculture medium increased the number of tolerant strains significantly in 0.1 ml of subcultured broth, demonstrating that the detection of penicillin-tolerant viridans group streptococci might be hampered by the carry-over of penicillin.