bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphorylation of acyclovir in vitro in activated Burkitt somatic cell hybrids
Authors: Datta A K , Pagano J S
Published: June 2012

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] (ACV), a potent antiviral compound, was phosphorylated to the same extent by extracts from untreated and iododeoxyuridine-treated Epstein-Barr virus-containing latent D98/HR-1 somatic hybrid cells. ATP was the preferred phosphate donor over other nucleoside triphosphates. The cytosol extract from D98/HR-1 cells effected optimum phosphorylation of thymidine at pH 8.0, whereas ACV was phosphorylated equally well over a wide pH range. Electrophoretic analysis of thymidine kinase-, deoxycytidine kinase-, and ACV-phosphorylating activities from both untreated and iododeoxyuridine-treated cell extracts displayed identical properties. A small part (5 to 10%) of the loaded ACV-phosphorylating activity seemed to migrate with the deoxycytidine kinase activity from cytosol. dTTP and dCTP, at relatively high concentrations, partially inhibited ACV-phosphorylating activity. The results suggest that Epstein-Barr virus does not code for its own thymidine kinase and that phosphorylation of ACV in Epstein-Barr virus-producing cells is carried out by multiple or as yet unidentified ATP-dependent nonspecific cellular phosphotransferases.
Interferon susceptibility of herpes simplex virus strains isolated from patients enrolled in clinical trials
Authors: Armstrong J A , Skicki-Mullen M B , Breinig M K , Ho M
Published: June 2012

Herpes simplex virus type 1 strains isolated from patients who had received interferon in a clinical trial were not more resistant to human leukocyte interferon than strains derived from recipients of a placebo. The susceptibility of herpes simplex virus type 2 strains isolated from herpes genitalis was slightly less than that of herpes simplex virus type 1 strains causing herpes genitalis.
Pharmacology of aztreonam after intravenous infusion
Authors: Scully B E , Swabb E A , Neu H C
Published: June 2012

The pharmacokinetics of aztreonam, a monocyclic beta-lactam which inhibits most members of the family Enterobacteriaceae at concentrations of less than 1 microgram/ml and most Pseudomonas aeruginosa isolates at concentrations of less than 16 micrograms/ml, were examined in healthy male volunteers after 30-min intravenous infusions of 0.5, 1, and 2 g of the drug. Mean peak levels of the drug in serum at the end of infusion were 65.5, 164, 255 micrograms/ml after 0.5 1, and 2 g, respectively, with levels of the drug in serum of 1.8, 3, and 8.5 micrograms/ml at 8.5 h for the three doses, respectively. The half-life was approximately 2 h for all three doses. The total serum clearance averaged 1 ml/min per kg. The apparent volume of distribution averaged 0.17 liter/kg for the three doses. Overall excretion of the drug in urine was 61%, with mean levels in urine of 23, 52, and 109 micrograms/ml at 8.5 to 12.5 h after 0.5, 1, and 2 g of aztreonam, respectively. Concentrations of the drug in serum after a 1-g dose exceeded the minimal inhibitory concentration for 90% of the members of the Enterobacteriaceae by four- to eightfold for 8 h and exceeded the minimal inhibitory concentration for P. aeruginosa isolates for 4 h.
Metabolic fate of [14C]SM-1652, a new antipseudomonal cephalosporin, after parenteral administration to rats
Authors: Imasaki H , Enjoji Y , Matsui H , Kawai R , Kawamura S , Okuda T
Published: June 2012

A study of the metabolic fate of [14C]SM-1652 after intravenous or intramuscular injection into rats showed that: (i) the elimination of the labeled compound from the blood was the same after intravenous and intramuscular injections; (ii) the radiolabeled drug was distributed rapidly and widely after intravenous administration with the highest concentration in the kidney and the lowest in the brain; (iii) placental transmission was slight, as it was passed into the milk, where the concentration was about 14% that of plasma; (iv) 33 and 67% of the administered radioactivity was excreted in urine and feces, respectively; (v) radioactivity in both urine and bile was ascribable to unaltered SM-1652; and (vi) upon repeated intramuscular injections twice daily, levels of labeled SM-1652 in tissue increased gradually, reaching a plateau at the 11th injection.
Pharmacokinetics of ceftizoxime in subjects with various degrees of renal function
Authors: Kowalsky S F , Echols R M , Venezia A R , Andrews E A
Published: June 2012

The pharmacokinetics of ceftizoxime (FK-749) were studied in 20 volunteers with various degrees of renal function. Creatinine clearances ranged from zero to 157 ml/min per 1.73 m2. One gram of ceftizoxime was administered by a 30-min drip infusion, and blood and urine samples were collected for up to 48 h after drug administration. For volunteers with a creatinine clearance of greater than or equal to 80 ml/min per 1.73 m2 (group I), the mean half-life was 1.65 h, whereas for volunteers with a creatinine clearance of less than 10 ml/min per 1.73 m2 (group IV), the half-life was 34.7 h. The volume of distribution at steady state (Vdss) and the volume of distribution area (Vdarea) were calculated for each group and ranged from 0.377 to 0.263 and 0.421 to 0.264 liters/kg for groups I and IV, respectively. Total body clearance of ceftizoxime correlated with creatinine clearance (r = 0.953), and the mean urinary recovery of unchanged drug in normal volunteers was 72.4%. A 4-h hemodialysis procedure reduced serum ceftizoxime concentrations by approximately 52%; however, serum concentrations at 48 h after drug administration were still greater than 10 micrograms/ml in dialysis subjects. By using the relationship between total body clearance of ceftizoxime and creatinine clearance, a nomogram was developed to assist in the administration of ceftizoxime to patients with renal dysfunction.
Sodium hypochlorite decontamination of split-thickness cadaveric skin infected with bacteria and yeast with subsequent isolation and growth of basal cells to confluency in tissue culture
Authors: Fader R C , Maurer A , Stein M D , Abston S , Herndon D N
Published: June 2012

The ability of sodium hypochlorite to decontaminate skin while leaving sufficient epidermal cell viability for growth in tissue culture was investigated with an in vitro system. Split-thickness cadaveric skin was infected with Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans and subsequently treated with various concentrations of sodium hypochlorite for various time intervals. Exposure to a 0.5% solution of sodium hypochlorite for 6 min effectively decontaminated the skin while leaving 66% of the basal cells viable. The basal cells were subsequently grown to confluency in tissue culture. This study demonstrates that microbial colonization of skin can be eliminated by exposure to dilute hypochlorite. This procedure, while decontaminating the skin, leaves sufficient viability of epidermal cells for subsequent growth and expansion in tissue culture, elements essential for grafting over wounds.
Production of a bacteriocin, ulceracin 378, by Corynebacterium ulcerans
Authors: Abrehem K , Zamiri I
Published: June 2012

The production of the bacteriocin ulceracin 378 by Corynebacterium ulcerans 378 was demonstrated during the growth of the organism on solid medium. Ulceracin 378 was not found in broth cultures and could not be extracted from the organisms by various solvents and salt solutions. Ulceracin 378 was not inducible by UV irradiation or mitomycin C treatments. Ulceracin 378 was active against all of the C. ulcerans strains tested and some related species, but it was not autoinhibitory. The active material was not phage related and was extracted from cultures grown on semisolid media composed of proteose peptone, Tween 80, Casamino Acids, glycerol, and sodium chloride. The yield was significantly reduced by either increasing the agar concentration or omitting Tween 80. Ulceracin 378 was resistant to DNase, RNase, phospholipases C and D, and alkaline phosphatase but was susceptible to proteolytic enzymes. This suggests that the active principle of ulceracin is protein in nature. Ulceracin 378 was partially purified by ammonium sulfate fractionation, dialysis, and chromatography on DEAE-cellulose.
Antiviral effects of hygromycin B, a translation inhibitor nonpermeant to uninfected cells
Authors: Lacal J C , Carrasco L
Published: June 2012

Hygromycin B, a preferential translation inhibitor in virus-infected cells, has been tested for its antiviral effects against herpes simplex virus type 2 and poliovirus. The activity has been compared with other antiviral agents such as vidarabine and iododeoxyuridine.
Intraperitoneal penetration of cefotetan
Authors: Wise R , Donovan I A , Drumm J , Dent J , Bennett S A
Published: June 2012

The intraperitoneal penetration of cefotetan was studied after a 1-g intravenous injection in 25 patients undergoing elective gastrointestinal surgery. Levels of peritoneal fluid were high within 10 min after administration and increased to 44% of the serum levels after 30 min, rising to 115% at 3 h. The mean concentration of cefotetan between 3 and 5 h after administration was 32.3 micrograms/ml. These findings suggest that 1 g of cefotetan administered before abdominal surgery would result in intraperitoneal cefotetan levels necessary to inhibit susceptible pathogens for 5 h or more.
Antimicrobial activity and other in vitro properties of cefoperazone A, the principal metabolite of cefoperazone sodium
Authors: Jones R N , Barry A L
Published: June 2012

Cefoperazone A, the principal metabolite of cefoperazone, was found to have an antimicrobial activity ranging from slightly below to 16-fold less than that of the parent drug. Like cefoperazone, the metabolite is bactericidal, penetrates well into bacterial cells, and has moderate beta-lactamase stability, some strains of members of the family Enterobacteriaceae produce an inoculum effect on the metabolite activity.
Analysis of penicillin N ring expansion activity from Streptomyces clavuligerus by ion-pair high-pressure liquid chromatography
Authors: Jensen S E , Westlake D W , Wolfe S
Published: June 2012

An ion-pair, reversed-phase, high-pressure liquid chromatographic method for the analysis of penicillin N ring expansion activity has been developed which allows simultaneous measurement of both substrate and product. The high-pressure liquid chromatography conditions were as follows: stationary phase, C18; flow rate, 2 ml/min; detection, 220 nm. The stationary phase was preconditioned with 4.5 mM tetrabutylammonium bromide in 0.05 M KH2PO4 (pH 4.0)-methanol (85:15, vol/vol) and then equilibrated with 0.06 mM tetrabutylammonium bromide in 0.05 M KH2PO4 (pH 4.0)-methanol (95:5, vol/vol) for analysis of reaction mixtures. These conditions separated authentic samples of penicillin N and desacetoxycephalosporin C and allowed cell-free studies of the ring expansion of penicillin N to desacetoxycephalosporin C by a partially purified enzyme from Streptomyces clavuligerus to be followed conveniently.
Synergistic antiviral activity of acyclovir and interferon on human cytomegalovirus
Authors: Smith C A , Wigdahl B , Rapp F
Published: June 2012

The efficacy of human alpha interferon (IFN-alpha) combined with 9-(2'-hydroxyethoxymethyl)guanine (acyclovir; ACV), (E)-5-(2-bromovinyl)-2'-deoxyuridine, 9-beta-D-arabinofuranosyladenine, or 1-beta-D-arabinofuranosylcytosine on the inhibition of human cytomegalovirus (HCMV) replication in human embryonic lung cells was analyzed by plaque reduction assays. IFN-alpha combined with 9-beta-D-arabinofuranosyladenine or 1-beta-D-arabinofuranosylcytosine produced an additive antiviral activity with respect to HCMV plaque formation. IFN-alpha combined with (E)-5-(2-bromovinyl)-2'-deoxyuridine also exhibited additive antiviral activity. However, IFN-alpha combined with ACV at concentrations higher than 10 microM consistently yielded synergistic activity in HCMV plaque reduction assays. Kinetic analyses of HCMV replication demonstrated that approximately a 1,000-fold reduction can be attained through the synergistic interaction between ACV (200 microM) and IFN-alpha (42 IU/ml). These data suggest that combined ACV and IFN-alpha treatment may be useful against HCMV infection.
Determination of ceftazidime in biological fluids by using high-pressure liquid chromatography
Authors: Myers C M , Blumer J L
Published: June 2012

Ceftazidime is a new beta-lactamase-stable third-generation cephalosporin with a broad spectrum of antimicrobial activity. To evaluate the biodisposition of the drug in infants and children, a rapid and simple high-pressure liquid chromatographic technique was developed. The method is useful for both serum and urine and involves methanol precipitation followed by reverse-phase chromatography on MicroPak MCH 10. The mobile phase, consisting of 20% methanol and an 80% aqueous solution of 50 mM ammonium dihydrogen phosphate and 117 microM perchloric acid, is pumped at 1 ml/min through the column which is maintained at 50 degrees C. The drug was detected at 257 nm with a variable-wavelength UV detector. A good linear correlation was observed between the peak area and the ceftazidime concentration at 0.3 to 500 micrograms/ml (r = 0.999). Since an equal volume of cold methanol is used to precipitate proteins from serum samples and only 20 microliters of the resultant supernatant is injected into the column, samples as small as 50 microliters may be routinely analyzed. This method has been used to study ceftazidime pharmacokinetics in more than 30 patients and has proven to be rapid and reproducible.
Minimal inhibitory concentrations of various antimicrobial agents for human oral anaerobic bacteria
Authors: Baker P J , Slots J , Genco R J , Evans R T
Published: June 2012

The minimal inhibitory concentrations of a series of antimicrobial agents for human oral organisms were determined under anaerobic growth conditions by an agar dilution assay. With the exception of black-pigmented Bacteroides spp., minimal inhibitory concentrations for oral isolates were similar to those for non-oral isolates of organisms of the same or closely related species.
In vitro activity of amoxicillin in combination with clavulanic acid against Mycobacterium tuberculosis
Authors: Cynamon M H , Palmer G S
Published: June 2012

The comparative in vitro activity of amoxicillin alone and in combination with clavulanic acid against 15 isolates of Mycobacterium tuberculosis was evaluated by broth dilution susceptibility testing. Amoxicillin inhibited 4 of 15 isolates at 8 micrograms/ml or less but was not bactericidal against any of the isolates at that concentration. Amoxicillin in combination with clavulanic acid was bactericidal for 14 of 15 isolates tested at an amoxicillin concentration of 4 micrograms/ml or less and a clavulanic acid concentration of 2 micrograms/ml or less.
Minimal inhibitory concentrations of 19 antimicrobial agents for 96 clinical isolates of group IVe bacteria
Authors: Welch W D , Porschen R K , Luttrell B
Published: June 2012

Susceptibility testing of 96 clinical group IVe isolates to 19 antimicrobial agents by agar dilution revealed that, at drug levels achievable in serum, the isolates were susceptible only to aminoglycosides, cephalosporins, and colistin, whereas at drug concentrations attainable in urine, they were susceptible to erythromycin, tetracycline, and nitrofurantoin as well.
Comparison of the efficacy of vidarabine, its carbocyclic analog (cyclaradine), and cyclaradine-5'-methoxyacetate in the treatment of herpes simplex virus type 1 encephalitis in mice
Authors: Shannon W M , Westbrook L , Arnett G , Daluge S , Lee H , Vince R
Published: June 2012

The relative therapeutic effects of vidarabine (9-beta-D-arabinofuranosyladenine), cyclaradine (the adenosine deaminase-resistant carbocyclic analog of vidarabine), and cyclaradine-5'-methoxyacetate in the parenteral treatment of systemic herpes simplex virus type 1 infections in Swiss mice were determined. Among control mice inoculated intraperitoneally with virus, a mortality rate of 95% was observed. The intraperitoneal administration of nontoxic doses of vidarabine (125 to 250 mg/kg per day) or cyclaradine (113 to 450 mg/kg per day), by daily injections for 7 days beginning 4 h after virus inoculation, reduced mortality to 0 to 10%. Among control animals inoculated intracerebrally with 32 50% lethal doses of virus, 100% mortality was observed, with a mean survival time of 4.6 days. Treatment with either drug at equimolar dose levels ranging from ca. 32 to 750 mg/kg per day produced significant (P less than 0.0005), dose-dependent increases in the mean survival time of animals dying of herpesvirus encephalitis. Mice inoculated intracerebrally with 10 50% lethal doses of virus exhibited 97% mortality and a mean survival time of 5.5 to 6.4 days. Treatment with vidarabine, cyclaradine, or cyclaradine-5'-methoxyacetate significantly increased the mean survival time of dying animals and, at doses ranging from 250 to 750 mg/kg per day, produced significant increases in survival. The three drugs displayed equivalent antiviral efficacy in vivo. Drug toxicity (measured by weight loss) was not detected in mice treated with cyclaradine or cyclaradine-5'-methoxyacetate at 750 mg/kg per day, whereas severe toxicity (weight loss of greater than or equal to 3 g) was observed in mice treated with vidarabine at an equivalent dose level. Thus, cyclaradine or its 5'-methoxyacetic acid ester may possess some advantage over vidarabine in the treatment of severe herpesvirus infections and should therefore be considered for clinical trials in humans.
Susceptible Escherichia coli cells can actively excrete tetracyclines
Authors: McMurry L M , Aronson D A , Levy S B
Published: June 2012

Escherichia coli shows severalfold less susceptibility to tetracyclines when grown in enriched medium than in minimal medium. Transport studies with cells harvested from these media showed different handling of the drugs. Whereas an energy-dependent uptake of tetracycline and minocycline was observed in susceptible K-12 and wild-type E. coli strains grown in minimal medium, an active efflux of minocycline and, to a lesser extent, tetracycline was seen in cells grown in L broth and other enriched media. This efflux was replaced by an active uptake system after treatment of cells grown in L broth with EDTA. When assayed at a lower temperature (27 degrees C), even cells grown in minimal medium showed an efflux of minocycline. Everted membrane vesicles prepared from susceptible cells grown in minimal medium or L broth showed an energy-dependent accumulation of minocycline and tetracycline when supplied with certain divalent cations. These results suggest that an active efflux of tetracyclines occurs in susceptible E. coli but is not detected in cells grown in minimal medium because greater permeability of the outer membrane allows a more rapid active uptake. This efflux system is distinct from that specified by tetracycline resistance determinants. Since the active efflux of minocycline in cells grown in L broth disappeared at external antibiotic concentrations of greater than 100 microM, it may be saturable and so mediated by a membrane carrier.
Comparison of ketoconazole and amphotericin B in interference with thymidine uptake by and blastogenesis of lymphocytes stimulated with Histoplasma capsulatum antigens
Authors: Alford R H , Cartwright B B
Published: June 2012

Human peripheral blood lymphocytes stimulated with Histoplasma capsulatum yeasts were exposed in culture to graded concentrations of ketoconazole or amphotericin B and subsequently assessed for membrane integrity, thymidine uptake, and blastogenesis. Lymphocyte reactivity varied with concentration and duration of exposure to ketoconazole. Overt membrane toxicity resulted from exposure to 40 micrograms of ketoconazole per ml for 5 days, diminished thymidine uptake occurred with concentrations as low as 5 micrograms/ml, and 15 to 20 micrograms/ml caused a marked decrease in thymidine uptake and eventually diminished blastogenesis. The antilymphocyte action of ketoconazole was neutralized by increasing the concentration of human serum in cultures to 40% regardless of its cholesterol content. Amphotericin B activity was qualitatively similar but less pronounced.
Extravascular penetration of tobramycin and netilmicin in a subcutaneous visking chamber model in rabbits
Authors: Larson T A , Gerding D N , Peterson L R
Published: June 2012

Netilmicin and tobramycin penetration in a rabbit Visking chamber model was studied after administration of multiple intramuscular doses of 2 mg of either drug per kg every 4 h in a double-crossover design. The mean serum half-life, mean peak concentration in serum, and mean area under the plasma concentration curve were similar. The mean peak concentration in the chamber and mean area under the plasma concentration curve were likewise not significantly different.
In vitro antimicrobial susceptibility of penicillinase-producing and intrinsically resistant Neisseria gonorrhoeae strains
Authors: Cohen M S , Cooney M H , Blackman E , Sparling P F
Published: June 2012

The in vitro susceptibility of penicillinase-producing and intrinsically resistant Neisseria gonorrhoeae strains to 13 antimicrobial agents was tested. Regardless of the type of resistance, these organisms remained quite susceptible to newer cephalosporin agents, including moxalactam, cefoperazone, cefotaxime, and ceftazidime.
Comparison of flow cytometric analysis and [3H]thymidine incorporation for measurement of the effects of drug toxicity on lymphocyte stimulation
Authors: Marmer D J , Steele R W
Published: June 2012

Human mononuclear cells were exposed to three antiviral agents, stimulated with phytohemagglutinin, and assayed for DNA synthesis with [3H]thymidine uptake and flow cytometric analysis. Cytosine-arabinoside demonstrated inhibition of blastogenic reactivity by both [3H]thymidine uptake and flow cytometric analysis, whereas acyclovir showed no significant suppression. In contrast, (E)-5-(2-bromovinyl)-2'-deoxyuridine, a thymidine analog, demonstrated a lack of correlation between the two methods. The competitive inhibition of some compounds with [3H]thymidine incorporation necessitates the use of other methods to measure DNA synthesis.
Efficacy and safety of ceftriaxone in serious pediatric infections
Authors: Aronoff S C , Murdell D , O'Brien C A , Klinger J D , Reed M D , Blumer J L
Published: June 2012

Thirty-four patients aged 1 month to 19 years were treated with ceftriaxone for suspected bacterial infections. Bacterial pathogens were isolated from 25 children. The overall bacterial cure rate was 88%, with an overall clinical response rate of 96%. No side effects requiring cessation of therapy were observed. Ceftriaxone proved to be safe and effective in the treatment of serious infections in children.
Amoxicillin combined with clavulanic acid for the treatment of soft tissue infections in children
Authors: Fleisher G R , Wilmott C M , Campos J M
Published: June 2012

We compared responses to amoxicillin combined with clavulanic acid (ACA) with a cefaclor regimen in children with skin and soft tissue infections (impetigo and cellulitis) due to Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus species. All isolates from the 41 patients we were able to evaluate were susceptible to ACA by disk susceptibility testing at the onset of treatment. The 21 children receiving ACA and 18 (90%) of 20 taking cefaclor responded to therapy. Clinical cure was achieved in 18 (86%) of 21 and 18 (90%) of 20 in the two groups, respectively. Bacteriological failure occurred in 2 (10%) patients in the cefaclor group and none in the group receiving ACA; however, there were 2 (9%) relapses and 1 (5%) reinfection among the 21 children taking ACA. Adverse effects, although mild, occurred more commonly (9 of 21 versus 1 of 20; P = 0.005) with ACA than with cefaclor.
Sensitive radioimmunoassay for the broad-spectrum antiviral agent ribavirin
Authors: Austin R K , Trefts P E , Hintz M , Connor J D , Kagnoff M F
Published: June 2012

Ribavirin, 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxyamide (Virazole; Viratek, Inc., Covina, Calif.), has a broad spectrum of antiviral activity. However, the study of the absorption, metabolism, and excretion of this compound has been limited by the lack of an appropriate assay for ribavirin and its metabolites. Since ribavirin has definite potential for therapeutic use, we developed a radioimmunoassay to measure ribavirin levels in clinical specimens. To prepare an effective immunogen, ribavirin was monosuccinylated and coupled to ovalbumin. The competitive binding radioimmunoassay, in which tritium-labeled ribavirin and rabbit antiribavirin serum were used, was quantitative for ribavirin at concentrations of 1 pmol/100 microliter in urine or plasma samples. The rabbit antibody cross-reacted with the major metabolite of ribavirin, 1,2,4-triazole-3-carboxamide, at a low level (2 to 5%) which did not interfere with ribavirin binding until concentrations of 1,2,4-triazole-3-carboxamide 10- to 100-fold higher than ribavirin were present in mock samples, a condition not present in biological specimens. We used the ribavirin radioimmunoassay to determine the ribavirin concentration in mouse plasma after intraperitoneal administration, in the sera of adults from Sierra Leone after oral or intravenous administration for treatment of suspected Lassa fever, and in the sera of children in the United States after small-particle aerosol administration. Our experience with the radioimmunoassay indicates that it is sensitive, accurate, and reproducible. The assay will permit studies leading to a better understanding of the pharmacology and pharmacokinetics of this potentially useful antiviral drug.
Intranasal interferon as protection against experimental respiratory coronavirus infection in volunteers
Authors: Higgins P G , Phillpotts R J , Scott G M , Wallace J , Bernhardt L L , Tyrrell D A
Published: June 2012

In a double-blind, placebo-controlled study, self-administered intranasal human interferon alpha A produced by recombinant DNA technology was given both before and after virus challenge with a respiratory coronavirus. The incidence of colds, the severity of symptoms and signs, and virus replication were all reduced in subjects receiving interferon as compared with those given placebo.
Effects of antibiotic treatment of nonlactating dairy cows on antibiotic resistance patterns of bovine mastitis pathogens
Authors: Berghash S R , Davidson J N , Armstrong J C , Dunny G M
Published: June 2012

Antibiotic resistance patterns of the major groups of bovine mastitis pathogens (Streptococcus agalactiae, other streptococci, Staphylococcus aureus, and Staphylococcus epidermidis) were examined by determining the minimum inhibitory concentration (MIC) of 13 different antibiotics against bacterial isolates from dairy cattle. The bacterial strains were obtained from milk samples from each cow in 21 New York state dairy herd surveys. In 12 herd surveys (high antibiotic-use group), all 365 cows received antibiotic infusions into the udder at the cessation of each lactation cycle. The 324 animals in the other nine herd surveys (low antibiotic-use group) did not routinely receive antibiotics during the nonlactation period. The MICs from the two groups were compared by calculating for each bacterial group the average MIC, the antibiotic concentration necessary to inhibit 90% of the isolates, and the antibiotic concentration necessary to inhibit 50% of the isolates. Increased resistance to all 13 antibiotics was observed with Streptococcus agalactiae isolates from the high antibiotic use herds. However, there was relatively little difference between the two groups in the resistance patterns of the other bacterial species examined. The most important finding of the study was the identification of a multiple beta-lactam resistance phenotype in Streptococcus agalactiae.
Pharmacokinetics and tissue penetration of ciprofloxacin
Authors: Crump B , Wise R , Dent J
Published: June 2012

A 500-mg dose of the quinoline ciprofloxacin was administered orally to each of six healthy male volunteers, after which the concentrations of this agent in serum and blister fluid were measured. Absorption appeared to be rapid, with a mean peak level of 2.4 micrograms/ml attained 1.25 h after administration. The serum elimination half-life was 3.9 h. The agent penetrated blister fluid well, the percent penetration being 57%. Urinary recovery of ciprofloxacin was 30%.
Effects of (E)-5-(2-bromovinyl)-2'-deoxyuridine on proliferation of human fibroblasts, peripheral blood mononuclear cells, and granulocyte-monocyte progenitor cells in vitro
Authors: Wittek A E , Cohen P S , Arvin A M , Smith S D , Koropchak C M , De Clercq E
Published: June 2012

Inhibition of human fibroblasts, granulocyte-monocyte progenitor cells, and lymphocytes was observed at (E)-5-(2-bromovinyl)-2'-deoxyuridine concentrations ranging from 21 to 197 micrograms/ml. These concentrations were 10- to 100-fold above usual serum concentrations after oral administration. (E)-5-(2-Bromovinyl)-2'-deoxyuridine compares favorably with currently used antivirals in terms of in vitro myelotoxicity and immunotoxicity.
Crossover study of the pharmacokinetics of ceftriaxone administered intravenously or intramuscularly to healthy volunteers
Authors: Meyers B R , Srulevitch E S , Jacobson J , Hirschman S Z
Published: June 2012

The pharmacokinetics of ceftriaxone were investigated in six healthy adults. One-gram doses were administered either intramuscularly or intravenously in a crossover design study. Mean peak ceftriaxone concentrations in plasma of 79.2 and 123.2 micrograms/ml were achieved with intramuscular injection and intravenous infusion, respectively, with plasma half-lives of 5.4 and 5.8 h. The urinary recovery of ceftriaxone in the first 24 h was 37% after intravenous infusion and 25% after intramuscular injection.
Comparative activities of Bay n7133, ICI 153,066, and ketoconazole in murine cryptococcosis
Authors: Graybill J R , Kaster S R , Drutz D J
Published: June 2012

Two new antifungal triazoles, BAY n7133 and ICI 153,066, were compared with ketoconazole in treatment of mice challenged intraperitoneally with Cryptococcus neoformans. At high challenge doses, thymus-containing normal mice had prolonged survival after treatment with BAY n7133. Athymic mice, which have severely deficient cell-mediated immunity, were not protected. At low challenge doses, athymic mice also had prolonged survival. Although BAY n7133 was protective, it was less effective than either ketoconazole or ICI 153,066. BAY n7133 was also less effective in mice challenged intracerebrally than in those challenged intraperitoneally. Both ketoconazole and ICI 153,066 prolonged survival and lowered cryptococcal spleen counts to a greater extent than did BAY n7133.
Frequency of tetracycline resistance determinant classes among lactose-fermenting coliforms
Authors: Marshall B , Tachibana C , Levy S B
Published: June 2012

Using colony hybridization techniques and DNA probes derived from four distinct tetracycline resistance determinants, we have examined the frequency of these determinants among 225 lactose-fermenting coliforms isolated from fecal samples of both humans and animals. The class B, or Tn10-type determinant, occurred most frequently at 73.3%, followed by class A (on RP1) at 21.7%, and class C (on pSC101) at 8%; 3.5% of isolates harbored two of these determinants. Hybridization to class D, carried by plasmid RA1, was not found among any of the isolates. One isolate failed to hybridize to any of the probes and represents a fifth class of determinant. No dramatic differences were observed in the frequencies of these determinants among four populations examined: hospital, urban, rural, and laboratory. At low stringency conditions of hybridization we were able to demonstrate cross-hybridization of determinant A with class C DNA and limited reaction with class B DNA, but no reaction with class D DNA.
Double-blind comparative study of two dosage regimens of cefaclor and amoxicillin-clavulanic acid in the outpatient treatment of soft tissue infections
Authors: Pien F D
Published: June 2012

A total of 88 patients were enrolled in a double-blind comparison of cefaclor and amoxicillin-clavulanic acid for the outpatient treatment of soft tissue infections (abscesses, cellulitis, and impetigo). In 84 clinically evaluable patients, high cure rates were obtained for all treatment groups (64 to 85%). Patients who received amoxicillin-clavulanic acid had a much higher incidence of gastrointestinal side effects than did patients who received cefaclor (34 versus 3%, P less than 0.005). However, only five patients with gastrointestinal reactions to amoxicillin-clavulanic acid had symptoms severe enough to warrant halting the completion of antibiotic therapy.
Selective decontamination of the digestive tract by pipemidic acid
Authors: Muytjens H L , van Veldhuizen G L , Welling G W , van der Ros-van de Repe J , Boerema H B , van der Waaij D
Published: June 2012

The possible use of pipemidic acid for preventing infections in granulocytopenic patients by selective elimination of the gram-negative rods from the digestive tract was evaluated. Fecal samples were collected before, during, and after therapy from 23 adults who were undergoing treatment of urinary tract infections with pipemidic acid at a dosage of 200 mg orally four times daily for 10 days. The concentration of pipemidic acid in the majority of the stool samples tested was 220 to 600 micrograms/g. However, in 19% of the samples collected on day 5, the concentration was below the detection limit (23 micrograms/ml). Approximately 90% of the fecal samples collected during or shortly after therapy were negative for members of the family Enterobacteriaceae. Resistance of the gastrointestinal tract against colonization by microorganisms from the environment (so-called colonization resistance) remained unimpaired, as measured by the absence of beta-aspartylglycine in the stool.
Cyclosporin A inhibits Coccidioides immitis in vitro and in vivo
Authors: Kirkland T N , Fierer J
Published: June 2012

BALB/c mice infected intraperitoneally with Coccidioides immitis were treated with cyclosporin (CyA) subcutaneously. CyA prevented infection when treatment was started at day zero. When treatment was delayed until day 6 after infection, the mice that received either 75 or 25 mg/kg per day survived, but those treated with 7.5 mg/kg per day had the same mortality rate as controls. The higher doses of CyA prevented dissemination of the fungus from the peritoneum to the lung but did not eliminate the peritoneal infection. In vitro, CyA inhibited the growth of the mycelial phase of eight test strains of C. immitis at a concentration of 1.0 microgram/ml. One or two strains of 10 other fungi were tested for susceptibility to CyA; only Aspergillus niger was inhibited, at a concentration of 0.1 microgram/ml. CyA is structurally unrelated to the polyenes and imidazoles and has a very restricted spectrum of antifungal activity. CyA may represent a new class of antifungal agents with a novel mechanism of antifungal activity.
Comparison of the concentrations of ceftazidime in the serum of newborn infants after intravenous and intramuscular administration
Authors: Boccazzi A , Rizzo M , Caccamo M L , Assael B M
Published: June 2012

The concentrations of ceftazidime in serum were studied in 16 preterm and term neonates to whom a single dose of 50 mg/kg had been administered intramuscularly or intravenously. After intramuscular injection, concentrations of ceftazidime in serum were comparable to those obtained with the intravenous dose, although they were more variable. Peak serum levels ranging from 50 to 102 micrograms/ml were reached 30 to 60 min after intramuscular injection. The concentrations declined monoexponentially after the peak, with a mean half-life of 3.8 +/- 1.1 h. Concentrations of ceftazidime in serum declined biexponentially after intravenous injection, with a terminal half-life of 4.7 +/- 1.5 h.
Synthesis and biological activities of 4"-deoxy-4"-sulfonamido-oleandomycin derivatives
Authors: Bright G M , English A R , Nagel A A , Retsema J A , Sciavolino F C
Published: June 2012

Chemical modification of the macrolide antibiotic oleandomycin (C-1) is described. Reductive amination of 11-acetyl-4"-deoxy-4"-oxo-oleandomycin (C-6) with ammonium acetate provides amino-oleandomycin derivative C-7 in which the 4"-amine is oriented in the axial configuration. The structure-activity relationship of a series of 4"-sulfonamide analogs prepared from amino-oleandomycin derivative C-7 is discussed. Noteworthy is the significant in vitro potency enhancement of the para-chlorobenzenesulfonamide analog C-12 over that of the parent oleandomycin. The absolute configuration of the 4"-amino-oleandomycin derivative C-7 was established through X-ray analysis of the para-iodobenzenesulfonamide analog C-14.
In vitro activities of ciprofloxacin, norfloxacin, pipemidic acid, cinoxacin, and nalidixic acid against Chlamydia trachomatis
Authors: Heessen F W , Muytjens H L
Published: June 2012

The in vitro activities of five quinolinecarboxylic acids against two laboratory strains of Chlamydia trachomatis were compared. The minimal inhibitory concentrations of nalidixic acid, cinoxacin, and pipemidic acid were all greater than or equal to 50 micrograms/ml; the activity of norfloxacin was intermediate (minimal inhibitory concentration, 8 to 16 micrograms/ml). Ciprofloxacin was the most active of these drugs (minimal inhibitory concentration, 0.5 to 1 microgram/ml).
Hemodialysis elimination rates and clearance of gentamicin and tobramycin
Authors: Matzke G R , Halstenson C E , Keane W F
Published: June 2012

The apparent hemodialyzer elimination rate constant and clearance for gentamicin and tobramycin were determined during 100 routine hemodialysis treatments in 49 patients. Three different dialyzers (CDAK 3500, CF 1211, and CF 1511), which vary in membrane composition, surface area, and thickness, were evaluated. The elimination rate constant in each patient was calculated from the slope of the log serum concentration-time curves. Two different elimination rate constants for each patient were derived, one during hemodialysis (KT) and one off hemodialysis (K). The hemodialyzer elimination rate constant (KD) for each dialyzer was calculated as the difference between these two values. The hemodialyzer clearance (Cd) was calculated by multiplying the hemodialyzer elimination rate constant by the volume of distribution of the patient. The KDS of gentamicin and tobramycin by the three dialyzers were significantly different. The gentamicin KD of the CDAK 3500 was lower than the values of the CF 1211 and CF 1511 (0.086 versus 0.123 versus 0.131 h-1, respectively). The Cd of the CDAK 3500 for gentamicin was also significantly lower than that of the CF 1511. Although the CdS of tobramycin for the CF 1211 and CF 1511 were 24 and 43% greater than that for the CDAK 3500, these differences were not statistically significant. The KD and Cd of tobramycin were greater than those of gentamicin for all three dialyzers. These data demonstrate that commonly used hemodialyzers vary markedly with respect to their elimination and clearance characteristics of gentamicin and tobramycin. Clinically, these observations may be helpful in designing the correct dose of gentamicin and tobramycin to achieve maximum drug safety and efficacy in hemodialysis patients.
Comparative antibacterial activities of 7 alpha-methoxy cephalosporins and 7 beta-methoxyiminoacetamido cephalosporins against Bacteroides fragilis
Authors: Kesado T , Watanabe K , Asahi Y , Isono M , Ueno K
Published: June 2012

The in vitro antibacterial activities of the newly developed 7 alpha-methoxy cephalosporins and 7 beta-methoxyiminoacetamido cephalosporins against 67 clinical isolates of Bacteroides fragilis and their resistance to the hydrolytic action of a beta-lactamase produced by B. fragilis were simultaneously compared. The minimal inhibitory concentrations that inhibited 90% of the 7 alpha-methoxy cephalosporins, cefoxitin, cefmetazole, moxalactam, and cefotetan, against the isolates were 4, 8, 8, and 16 micrograms/ml, respectively, and these antibiotics were entirely resistant to hydrolysis by beta-lactamases (0.10 mumol/h per mg of protein) of the isolates. By contrast, 7 beta-methoxyiminoacetamido cephalosporins represented by cefotaxime, ceftizoxime, and cefmenoxime were not effective, as indicated by the minimal inhibitory concentrations that inhibited 90%, 64, 32, and 128 micrograms/ml, respectively. Their antibacterial activities clearly corresponded to their resistance to the hydrolytic action of the beta-lactamase: namely, the correlation coefficients in regression curves of cefotaxime, ceftizoxime, and cefmenoxime, which were expressed by the antibacterial activity (x axis) and the beta-lactamase activity (y axis) were 0.098, 0.034, and 0.163, respectively.
Antibacterial properties of tuftsin and its analogs
Authors: Blok-Perkowska D , Muzalewski F , Konopińska D
Published: June 2012

The antibacterial properties of tuftsin and its 11 analogs on 20 bacterial strains were investigated. Tuftsin showed a definite antibacterial effect at a minimal effective concentration of 62.5 micrograms/ml. All analogs were either less effective or lacked any activity. The bacteria used included some highly pathogenic organisms.
Concentrations of vancomycin in bone and serum of normal rabbits and those with osteomyelitis
Authors: Wilson K J , Mader J T
Published: June 2012

The concentrations of vancomycin in the bone and serum of rabbits with Staphylococcus aureus osteomyelitis were assessed after each rabbit was given a single dose of vancomycin. Simultaneous mean concentrations of vancomycin in infected rabbits 1 h after administration of the antibiotic were 36.4 +/- 4.6 micrograms/ml (serum), 5.3 +/- 0.8 microgram/g (infected bone), and 3.0 +/- 0.2 micrograms/g (noninfected bone). Concentrations of vancomycin in serum of normal controls were higher than concentrations of vancomycin in serum of osteomyelitic rabbits after 1, 2, 3, and 6 h.
Alpha-interferon administration in cytomegalovirus retinitis
Authors: Chou S W , Dylewski J S , Gaynon M W , Egbert P R , Merigan T C
Published: June 2012

Four patients, including three with the acquired immunodeficiency syndrome (AIDS), were treated with high-dose, buffy coat-derived alpha-interferon for progressive cytomegalovirus retinitis. Two of these patients had decreased viruria during therapy and the other two had increased viruria. There was evidence of progression of disease despite therapy in all patients, although the retinitis eventually became quiescent in the patient without AIDS. The severe immunosuppression encountered in AIDS patients complicates the management of cytomegalovirus and other opportunistic infections.
Pharmacokinetics of moxalactam in elderly subjects
Authors: Andritz M H , Smith R P , Baltch A L , Griffin P E , Conroy J V , Sutphen N , Hammer M C
Published: June 2012

The pharmacokinetics of moxalactam were studied in 19 male volunteers 60 years of age or older with normal liver function tests and a creatinine clearance of greater than or equal to 60 ml/min. Moxalactam was administered in single or multiple intravenous or intramuscular doses. Rapid and complete intramuscular bioavailability was demonstrated in a subgroup of the study population. The mean plasma half-life was 2.9 +/- 0.8 h for intravenous doses and 3.5 +/- 0.9 h for intramuscular doses. Average renal clearances of 0.04 liters/kg per h accounted for 74.0 +/- 15.0% of total plasma clearance. Moxalactam plasma clearance showed a statistically significant (P less than 0.01) correlation with measured and calculated creatinine clearance. The major differences in moxalactam pharmacokinetics seen in the elderly appear to be related to diminishing renal function and highly variable nonrenal elimination. Creatinine clearance can be used in estimating moxalactam doses in the elderly without significant renal impairment, but recommendations for the use of serum creatinine as an estimation of renal function or drug half-life are not valid in this population group.
Comparative efficacies of piperacillin, azlocillin, ticarcillin, aztreonam, and tobramycin against experimental Pseudomonas aeruginosa pneumonia
Authors: Schiff J B , Pennington J E
Published: June 2012

The therapeutic efficacies of the newer beta-lactam antibiotics piperacillin, azlocillin and aztreonam were compared with the efficacies of ticarcillin and tobramycin in a guinea pig model of experimental Pseudomonas aeruginosa pneumonia. For animals challenged with 2 X 10(8) CFU, tobramycin treatment resulted in survival rates and intrapulmonary killing of pseudomonads which were significantly greater than those found with any of the beta-lactam agents. There were no significant differences noted among the individual beta-lactam agents. When animals were challenged with 200-fold-fewer organisms (10(6) CFU), there was no significant difference between the efficacy of tobramycin and those of the various beta-lactams. These data suggest that tobramycin is particularly valuable in treating more severe P. aeruginosa pneumonia, whereas a number of different beta-lactam agents are of equivalent value in less severe lung infections.
Resistance trends of Neisseria gonorrhoeae in the Republic of Korea
Authors: Piziak M V , Woodbury C , Berliner D , Takafuji E , Kirkpatrick J , Opal S , Tramont E
Published: June 2012

Penicillinase-producing Neisseria gonorrhoeae has increased in the Far East to the point that penicillin can no longer be recommended as the drug of choice, mandating a change to spectinomycin. As part of an ongoing surveillance of antibiotic susceptibilities, minimal inhibitory concentrations of penicillin, tetracycline, spectinomycin, trimethoprim-sulfamethoxazole, cefoxitin, ceftriaxone, cefotaxime, and moxalactam were determined. A disturbing, steady increase in resistance to spectinomycin was documented.
Kinetic disposition of intravenous ceftriaxone in normal subjects and patients with renal failure on hemodialysis or peritoneal dialysis
Authors: Ti T Y , Fortin L , Kreeft J H , East D S , Ogilvie R I , Somerville P J
Published: June 2012

The kinetic disposition of a single intravenous dose of ceftriaxone (250 to 665 mg) was studied in six normal subjects and nine patients with renal insufficiency and normal hepatic function. In normal subjects, ceftriaxone was eliminated with a t1/2 beta of 5.2 h (range, 4.1 to 5.8). The total body clearance (Qb) was 13.5 ml/kg per h (range, 8.4 to 23.3), and renal clearance was 8.3 ml/kg per h (range, 5.8 to 13.3). In patients with severe renal insufficiency requiring peritoneal or hemodialysis, the mean t1/2 beta was prolonged to 13.4 h (range, 7.7 to 15.8) and the mean Qb was reduced to 6.9 ml/kg per h (range, 3.4 to 12.8). The apparent volumes of distribution (Vc and Vss) were not different from those determined in normal subjects. Peritoneal dialysis did not remove ceftriaxone. The dialysate of three patients on continuous peritoneal dialysis did not contain any measureable ceftriaxone, and the kinetic disposition in these patients was similar to the hemodialysis patients between their dialysis treatment. During a 4-h hemodialysis session, the total body clearance of ceftriaxone was reduced, perhaps secondary to a decrease in hepatic blood flow induced by the hemodialysis procedure. After a 12- or 24-h dose regimen, predicted trough concentrations of ceftriaxone in plasma at steady state derived from kinetic data generated from the study and assuming linear pharmacokinetic behavior were well above the minimum inhibitory concentrations of most sensitive bacteria, suggesting the feasibility of a once-a-day dosage regimen especially for patients with severe renal insufficiency.