bluuebunny/crossref_metadata_2025 huggingface dataset:
Alteration of lymphocyte transformation response to herpes simplex virus infection by acyclovir therapy
Authors: Lafferty W E , Brewer L A , Corey L
Published: June 2012

To evaluate the effect of acyclovir (ACV) therapy on the cellular immune response, we sequentially followed 43 patients with culture-proven first episodes of genital herpes simplex virus (HSV) infection. Twenty-three patients who were treated with ACV and 20 who received placebo had blood obtained weekly during the first 6 weeks after onset of lesions and had their in vitro lymphocyte transformation (LT) response to inactivated HSV antigens measured. The mean stimulation index to HSV antigens at week 3 among patients treated with systemic ACV was 3.5 +/- 0.64 compared to 18.4 +/- 6.89 in their placebo-treated counterparts (P less than 0.05). The mean time to the development of the peak LT response to HSV antigens was 4.3 weeks in systemic-treated versus 3.4 in placebo-treated patients (P less than 0.05). The time to the development of the peak in vitro LT response to HSV antigens and the height of that response were, however, similar between topical ACV- and topical placebo-treated patients. The geometric mean HSV-2-neutralizing titer in convalescent sera was 5.4 in recipients of systemic ACV compared to 10.0 in patients treated with systemic placebo (P less than 0.05). The LT response to HSV antigen was also measured at the first recurrence in 11 patients. No differences were found in the time to first recurrence, lesion duration, number of lesions, or mean stimulation index response to inactivated HSV antigens between the six patients treated with systemic ACV during their primary episode and the five given placebo during their primary episode. Systemic ACV therapy appears to diminish the peak in vitro LT response to inactivated HSV antigens as well as to delay the time to development of that peak response. However, the cell-mediated immune response to subsequent episodes appears similar.
Stimulatory, permeabilizing, and toxic effects of amphotericin B on L cells
Authors: Brajtburg J , Elberg S , Medoff J , Kobayashi G S , Schlessinger D , Medoff G
Published: June 2012

High concentrations of amphotericin B (AmB) killed mouse L cells, but low concentrations increased plating efficiency and stimulated the incorporation of labeled precursors into DNA and RNA. Thus, there were two disparate effects of AmB on L cells, stimulatory and toxic, and they occurred in distinct dose-related stages. AmB also affected the permeability of L cells. In dose-response studies, increases in cell membrane permeability, measured as the loss of K+ ions, occurred along with the stimulation of [3H]uridine incorporation into RNA. In contrast, stimulation of [3H]thymidine incorporation into DNA was only observed in cells recuperating from AmB-induced permeability changes. When the K+ concentration in the medium was lowered to 0.5 from 4.5 mM, or when 1 mM ouabain was added to the cultures, cell killing was potentiated, but the stimulatory and permeabilizing effects of subtoxic concentrations of AmB were unaffected. Furthermore, etruscomycin, a polyene antibiotic without any permeabilizing effects, nevertheless induced an enhancement of plating efficiency and of incorporation of [3H]uridine into RNA and [3H]thymidine into DNA. Our results suggest that the dose-related stimulatory, permeabilizing, and toxic effects of AmB most probably have distinct mechanisms of action and may be independent of one another.
Virucidal activity of glutaric acid and evidence for dual mechanism of action
Authors: Kuhrt M F , Fancher M J , McKinlay M A , Lennert S D
Published: June 2012

Rhinoviruses as a group are notably sensitive to inactivation in solutions with a pH of less than 5.3. Glutaric acid appears to possess virucidal activity in addition to the aciduant effect against rhinoviruses. A model system in which rhinovirus type 14 was incubated in the presence of glutaric acid (GA) (pH 4.0) at 0 degrees C was devised to separate intrinsic virucidal activity from the aciduant effect. Under these conditions, virucidal activity against rhinovirus type 14 was directly related to the concentration of GA present and the proportion of the acid in the diprotonated form. The virucidal activities of GA and several other compounds, including GA analogs and other mono- and dicarboxylic acids, were tested under the conditions described. In general, as the alkane bridge separating two carboxylic acid functions was lengthened, virucidal activity decreased. When 26 additional strains of rhinoviruses were tested in the model system, 19 were inactivated slowly enough to be compared. Of these, 63% were more susceptible to GA than to sodium acetate buffer and 26% were more susceptible to sodium acetate buffer. Eleven percent were resistant to both GA and sodium acetate buffer. The virucidal activity of GA for a majority of strains tested appeared to be due to combination of low pH and another mechanism of action presumably unrelated to pH.
Enhanced efficacy of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine in combination with alpha-interferon against herpes simplex virus type 2 in mice
Authors: Fraser-Smith E B , Eppstein D A , Marsh Y V , Matthews T R
Published: June 2012

The acyclic nucleoside DHPG [9-(1,3-dihydroxy-2-propoxymethyl)guanine] and recombinant human alpha-interferon of clones A/D potentiate each other's antiviral activity against a systemic infection with herpes simplex virus type 2. The effective dose at which 50% of the mice survived was lowered approximately 10-fold for DHPG when it was given in combination with a marginally effective dose of alpha-interferon and greater than 10-fold for alpha-interferon when it was given in combination with a nontherapeutic dose of DHPG.
Effect of aztreonam on throat and stool flora of cancer patients
Authors: Jones P G , Bodey G P , Swabb E A , Rosenbaum B
Published: June 2012

Eighteen patients with hematological malignancies received aztreonam in one of two dosing regimens, 1 or 2 g every 8 h for a total of 7 to 9 days. Throat and stool cultures were obtained before and during treatment with aztreonam. Aztreonam had little effect on the predominant throat flora. In contrast, facultatively anaerobic gram-negative bacilli were markedly decreased in stools during the administration of aztreonam. Strict anaerobes in the stool were variably affected by aztreonam.
Decreased biliary excretion of cefamandole after percutaneous biliary decompression in patients with total common bile duct obstruction
Authors: Levi J U , Martinez O V , Malinin T I , Zeppa R , Livingstone A , Hutson D , Calhoun P
Published: June 2012

The biliary penetration of cefamandole was studied in six patients with total biliary obstruction before and after placement of a transhepatic bile drainage catheter. Biliary levels of cefamandole remained depressed even when the drug was administered as late as 7 days after decompression of the biliary tract.
Susceptibility of Eikenella corrodens to penicillin, apalcillin, and twelve new cephalosporins
Authors: Goldstein E J , Citron D M
Published: June 2012

The susceptibility of 29 strains of Eikenella corrodens to penicillin, apalcillin, and 12 new cephalosporins was determined by the agar dilution method. Most strains were resistant to cefsulodin, and some were resistant to apalcillin and cefpiramide. Although all strains were susceptible to the other cephalosporins tested, most of those drugs were as active as or less active than penicillin. Susceptibility testing of isolates should be performed whenever a cephalosporin is used to treat infections involving E. corrodens.
Positive direct antiglobulin tests due to clavulanic acid
Authors: Williams M E , Thomas D , Harman C P , Mintz P D , Donowitz G R
Published: June 2012

Clavulanic acid, a beta-lactamase inhibitor, was found to be associated with the development of a positive direct antiglobulin test. Of 23 antibiotic courses in patients treated with ticarcillin, clavulanic acid, and tobramycin, 10 (43.5%) developed positive direct antiglobulin tests versus 2 of 26 (7.7%) patients treated with piperacillin and tobramycin (P = 0.0044). In vitro immunohematological studies showed that clavulanic acid caused a nonimmunologic adsorption of plasma proteins onto the erythrocyte surface. Hemolysis was not associated with such nonimmunologic adsorption. However, the resulting positive antiglobulin test might delay cross matching of blood products for transfusions or interfere with the evaluation of true immune-mediated hemolytic anemia.
Therapeutic efficacy of teicoplanin in experimental enterococcal endocarditis
Authors: Sullam P M , Täuber M G , Hackbarth C J , Sande M A
Published: June 2012

The antimicrobial activities of teicoplanin and ampicillin, alone and in combination with gentamicin, were compared in experimental Streptococcus faecalis endocarditis. Bacterial titers in vegetations of rabbits treated with teicoplanin were significantly lower than those of untreated controls (P less than 0.01) and were equivalent to titers in ampicillin-treated animals. Gentamicin increased the activities of both drugs to a comparable degree.
Pharmacokinetics of aztreonam in patients with gram-negative infections
Authors: Janicke D M , Cafarell R F , Parker S W , Apicella M A , Jusko W J
Published: June 2012

Aztreonam pharmacokinetics were assessed in seven patients treated for urinary (n = 6) or lower respiratory (n = 1) tract infections. Each patient was studied twice, at the beginning and end of therapy (7 to 10 days). The patients enrolled had normal to moderately impaired renal function; a good correlation (r2 = 0.90) between serum aztreonam clearance (CL) and creatinine clearance (CLCR) was observed (mean CL/CLCR ratio = 1.11). CL ranged from 21.6 to 121 ml/min per 70 kg, and the half-life ranged from 1.6 to 8.9 h. The mean steady-state volume of distribution (0.16 +/- 0.05 [standard deviation] liter/kg) approximated the extracellular fluid volume. Protein binding of aztreonam in serum (mean, 30%) was lower than that reported in healthy adults. CL increased significantly from the first to the last day of the study, probably reflecting increasing renal function. After multiple dosing (1 g every 8 h), no significant accumulation of aztreonam was observed. Overall, the disposition of aztreonam is comparable in infected and noninfected subjects, and dosing adjustments in patients with renal impairment should be facilitated by the good correlation between CL and CLCR.
Cloning and expression of Staphylococcus aureus plasmid-mediated quaternary ammonium resistance in Escherichia coli
Authors: Tennent J M , Lyon B R , Gillespie M T , May J W , Skurray R A
Published: June 2012

The Staphylococcus aureus plasmid pSK1 carries Tn4001, a 4.7-kilobase (kb) transposon which specifies resistance to gentamicin, tobramycin, and kanamycin. In addition, pSK1 mediates resistance to trimethoprim and linked resistance to ethidium bromide (Ebr) and to quaternary ammonium compounds (Qar). Restriction endonuclease analysis of pSK1 and a deleted derivative of pSK1 revealed that the gene(s) responsible for Ebr Qar lies within a 5.2-kb HindIII fragment. This fragment has been cloned into the Escherichia coli plasmid vector pBR322, and transformants of an E. coli K-12 strain exhibited Ebr Qar. Subcloning of the 5.2-kb insert, combined with data from electron microscopic analysis of deleted derivatives of pSK1, located the Ebr Qar determinant(s) on a 2.3-kb segment of pSK1 DNA.
Enhancement of the curative activity of primaquine by concomitant administration of mirincamycin
Authors: Schmidt L H
Published: June 2012

Mirincamycin, a lincomycin derivative with unequivocal but limited activity against the pre-erythrocytic and persisting exoerythrocytic stages of Plasmodium cynomolgi, has been evaluated for capacity to enhance the radical curative potential of the conventional primaquine-chloroquine combination. Established infections with sporozoites of the above plasmodium in rhesus monkeys served this evaluation. The results showed that the dose of primaquine required for cure of 50% of active infections was reduced by one-half to two-thirds by coadministration with 2.5 mg of mirincamycin per kg, 1/16 the 50% curative dose of this lincomycin derivative when used in a mono-drug regimen. The dimensions of the enhancement of the curative activity of primaquine were inversely related to the size of the sporozoite inoculum. The smallest dose of mirincamycin productive of enhancement was 2.5 mg/kg; whether doses larger than 2.5 mg/kg would have been more effective was not determined. There is much to be done before it is known whether a mirincamycin-primaquine combination is useful for suppressive cure or radical cure of the human malarias. Irrespective of that result, the current study serves to focus attention on a somewhat novel approach to the development of more effective and better-tolerated regimens for radical cure, an alternative to the empirical chemical synthesis and screening approach that has dominated searches heretofore.
Comparative in vitro activity of cefbuperazone against anaerobic bacteria isolated from community hospitals
Authors: Goldstein E J , Citron D M
Published: June 2012

The activity of cefbuperazone against 266 strains of anaerobic bacteria was determined by the agar dilution method and compared with cefoxitin, moxalactam, piperacillin, and clindamycin. All strains were recent clinical isolates from community hospitals. All agents tested showed good activity against Bacteroides fragilis, Fusobacterium spp., Propionibacterium spp., Clostridium septicum, Clostridium perfringens, and the anaerobic, gram-positive cocci and gram-negative cocci. Cefbuperazone, cefoxitin, and moxalactam had poor activity against Bacteroides thetaiotaomicron, Bacteroides ovatus, and Bacteroides distasonis. The susceptibility of other Clostridium spp., Lactobacillus spp., and Eubacterium lentum was variable. Our community hospital isolates showed a difference in susceptibility patterns from those reported from university and research centers. This supports the recommendation that clinical microbiology laboratories, including those in community hospitals, need to perform susceptibility testing on representative clinical isolates.
Once-daily ceftriaxone therapy for serious bacterial infections in children
Authors: Congeni B L , Chonmaitree T , Rakusan T A , Box Q T
Published: June 2012

Ceftriaxone administered as a single daily dose of 50 mg/kg was evaluated in the treatment of 35 children with a variety of nonmeningitic bacterial infections. In two of the patients, the drug was discontinued before the response to the drug could be evaluated. All of the remaining patients had a satisfactory response. In 22 of the patients, plasma was available for the determination of ceftriaxone levels 1 h after a dose and immediately before the next dose. All but one of these patients had trough ceftriaxone levels which exceeded the MIC of the infecting organism, although marginally so for Staphylococcus aureus. Ceftriaxone appears to be safe and effective in the treatment of a variety of bacterial pathogens in children when administered at a single daily dose of 50 mg/kg. This drug may be especially useful in those patients in whom outpatient antibiotic therapy is contemplated or in whom maintenance of intravenous access is difficult.
Structure-activity studies on phosphonoacetate
Authors: Mao J C , Otis E R , von Esch A M , Herrin T R , Fairgrieve J S , Shipkowitz N L , Duff R G
Published: June 2012

Phosphonoacetic acid is a selective antiherpesvirus agent. More than 100 congeners of phosphonoacetic acid were evaluated in vitro and in vivo to understand structure-activity relationships in the hope of designing a superior analog. Results showed that the antiherpesvirus activity had highly specific structural requirements. Neither the carboxylic nor the phosphono groups could be replaced. The distance between these two groups is important. Increase of this distance caused complete loss of activity. However, if this distance was maintained, the addition of groups to the methylene carbon resulted in a reduction, but not loss, of activity. On the other hand, decrease of the carbon chain to formic acid did not deteriorate its antiherpes activity. All analogs tested had lower activity than the parent compound. However, some compounds with decreased activity in vitro appeared to have favorable pharmacological properties in vivo.
Ineffectiveness and toxicity of BCG vaccine for the prevention of recurrent genital herpes
Authors: Douglas J M , Vontver L A , Stamm W E , Reeves W C , Critchlow C , Remington M L , Holmes K K , Corey L
Published: June 2012

One hundred fifty-five patients with genital herpes were enrolled in a double-blind, placebo-controlled trial comparing 0.1 ml of intradermal BCG vaccine with placebo for the prevention of recurrent episodes of genital herpes. The mean rate or recurrence over 9 months of prospective follow-up was 0.528 recurrences per month in BCG recipients compared with 0.392 recurrences per month in placebo recipients (not significant). The BCG vaccine also failed to influence the duration of lesions in the first recurrent episode of genital herpes after vaccination. Six patients were given a second inoculation of BCG vaccine, and persistent cutaneous granulomas were noted in three of these six patients. Intradermal inoculation with BCG does not appear to affect the natural history of genital herpes, and repeated inoculations can be toxic.
Relatedness of tetracycline resistance plasmids among species of coagulase-negative staphylococci
Authors: Cooksey R C , Baldwin J N
Published: June 2012

Four isolates of Staphylococcus aureus and 98 isolates of coagulase-negative staphylococci representing six species all obtained from endocervical cultures were examined for antimicrobial susceptibility and for the presence of plasmids. More than 80% of the isolates were susceptible to each of 12 antimicrobial agents tested, whereas only 33% were susceptible to penicillin G, 30% were susceptible to cadmium chloride, and 41% were susceptible to tetracycline. Although no species-related susceptibility or plasmid patterns were detected, 77 isolates contained at least one plasmid and 43 contained a plasmid similar in mass to a 2.7-megadalton tetracycline resistance plasmid previously reported in staphylococci. Association of tetracycline resistance with plasmids of this size in four species was determined from curing experiments. No plasmids homologous with the tetracycline resistance locus of the Escherichia coli plasmid pBR322 were found among 11 isolates examined by DNA hybridization. Homology with a 2.7-megadalton plasmids (pRC701) from an endocervical isolate of S. aureus, however, was apparent for 2.7-megadalton plasmids harbored by six isolates as well as with larger plasmids harbored by three isolates. Restriction analysis revealed that pRC701 shared structural identity with two plasmids of a similar mass from two species of coagulase-negative staphylococci as well as with a previously characterized tetracycline resistance plasmid originating in S. aureus.
Effectiveness of aztreonam for the treatment of gonorrhea
Authors: Gottlieb A , Mills J
Published: June 2012

Aztreonam, 1 g intramuscularly, was compared with spectinomycin, 2 g intramuscularly, for uncomplicated gonorrhea. There were no failures with either drug. For aztreonam, there were 26 urethral, 3 rectal, and 3 endocervical sites that were infected. Aztreonam in a single dose of 1 g intramuscularly is satisfactory therapy for uncomplicated urethral gonorrhea in men and may be effective for rectal and endocervical infection as well.
Isolation and preliminary characterization of erythromycin-resistant variants of Legionella micdadei and Legionella pneumophila
Authors: Dowling J N , McDevitt D A , Pasculle A W
Published: June 2012

Erythromycin-resistant Legionella spp. variants were obtained by a single passage of the naturally occurring bacteria on medium containing various concentrations of erythromycin. By disk diffusion susceptibility testing, at least three different phenotypic patterns of cross-resistance to macrolide, lincosamide, and streptogramin B antibiotics were observed among the 26 erythromycin-resistant strains examined.
In vitro activities of bismuth salts against rotaviruses and other enteric viruses
Authors: Ward R L , Sander D S , Knowlton D R
Published: June 2012

Bismuth salts inhibited plaque formation of all enteric viruses tested, which included four strains of rotavirus and one strain each of echovirus, reovirus, and poliovirus. The compounds had no direct virucidal effect at concentrations ranging from 0.025 to 2.5 mg/ml, and the inhibitory effects were observed only at concentrations slightly below those that caused extensive cytotoxicity. Plaque inhibition appeared to result from interference with host cell functions, with secondary inhibition of virus production.
Antimicrobial susceptibilities of anaerobic bacteria isolated from female genital tract infections
Authors: Hill G B , Ayers O M
Published: June 2012

Certain species or subspecies of anaerobic bacteria are isolated with higher frequency from female genital tract infections than from other anatomic sites. To gain susceptibility data more specific to the treatment of these infections, nine antimicrobial agents were tested by an agar dilution technique against 230 anaerobic bacteria isolated solely from obstetric and gynecological infections. These genital isolates were, in general, very susceptible to imipenem (most active, inhibiting all gram-negative rods at less than or equal to 1 microgram/ml), clindamycin (all isolates inhibited at less than or equal to 4 micrograms/ml), metronidazole (all gram-negative rods inhibited at less than or equal to 4 micrograms/ml), and chloramphenicol. Penicillin G had generally low activity against Bacteroides spp., not restricted to just the Bacteroides fragilis group, although it was very active against gram-positive species. Bacteroides bivius, a species uniquely common in female genital infections, was particularly resistant (90% MIC, 64 U/ml). Also, the Bacteroides melaninogenicus isolates were less susceptible than previously reported for isolates not exclusively from genital sites. Compared with moxalactam, cefotaxime, and cefoperazone, cefoxitin usually demonstrated equal or greater activity against most Bacteroides spp., with the exception of greater activity of moxalactam against B. fragilis (formerly subsp. fragilis). Resistance to moxalactam was observed among strains of Peptostreptococcus anaerobius, a common genital isolate. Overall, the activities of these four drugs were not as predictable as those observed for clindamycin, metronidazole, chloramphenicol, and imipenem.
Efficacy of intermittent versus continuous administration of netilmicin in a two-compartment in vitro model
Authors: Blaser J , Stone B B , Zinner S H
Published: June 2012

Several aminoglycoside dosage regimens were studied in a kinetic in vitro model. Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were exposed in serially placed artificial capillary units to netilmicin concentrations that changed based on human two-compartment pharmacokinetics. The same total dose per 24 h was administered as a continuous infusion (3.7 micrograms/ml) or in 1-h infusions given every 24 (24 micrograms/ml) or 8 h (8 micrograms/ml). The once daily administration showed the best response in terms of either faster killing of E. coli, K. pneumoniae, and S. aureus or greater reduction of the inocula of P. aeruginosa. After 28 h of treatment, however, all regimens reduced the nonpseudomonads by more than 99.99%, whereas all three P. aeruginosa strains regrew to greater than 10(8) CFU/ml due to selection of resistant subpopulations. In contrast to the bactericidal effect of the first dose, no killing occurred after subsequent doses if the ratio of peak drug concentration to MIC was low (less than or equal to 6). These results support the concept of administering high doses of aminoglycosides once every 24 h.
Comparison of high-pressure liquid chromatography and bioassay for determination of ciprofloxacin in serum and urine
Authors: Joos B , Ledergerber B , Flepp M , Bettex J D , Lüthy R , Siegenthaler W
Published: June 2012

Ciprofloxacin was given orally to 10 healthy volunteers for seven consecutive doses of 250 mg every 12 h. Serum and urine samples were collected at distinct times between 0 and 96 h and analyzed both by high-pressure liquid chromatography and by a microbiological assay. The detection limits were 0.006 and 0.03 microgram/ml, respectively. For each method, imprecision coefficients of variation were less than 6.1% at various concentrations in serum and urine. The means +/- standard deviations of the absolute values of the relative differences between the two methods were 9.3 +/- 6.8% (n = 225) for serum samples and 58.5 +/- 50.4% (n = 70) for urine samples. Comparison of the concentrations in serum measured with high-pressure liquid chromatography and bioassay by regression analysis yielded a slope which was not significantly different from 1.0 (99.9% confidence limits: 0.984 less than slope less than 1.035). In urine, however, the bioassay results were markedly higher than the high-pressure liquid chromatography values (1.327 less than slope less than 1.698), which indicates the presence of antimicrobially active metabolites. The cumulative 12-h urinary recovery after the first and seventh doses averaged 30.2 +/- 8.5 and 26.4 +/- 4.6%, respectively, by high-pressure liquid chromatography, whereas with bioassay 38.2 +/- 5.9 and 45.5 +/- 5.9% activity was recovered. Protein binding appeared to be neither concentration nor pH dependent and averaged 21.9 +/- 4.1%.
Role of beta-lactam hydrolysis in the mechanism of resistance of a beta-lactamase-constitutive Enterobacter cloacae strain to expanded-spectrum beta-lactams
Authors: Vu H , Nikaido H
Published: June 2012

Enterobacter cloacae strains producing chromosomally mediated beta-lactamase constitutively show high degrees of resistance to most of the third-generation beta-lactams. It has been proposed that this resistance is due to the nonhydrolytic binding or trapping of beta-lactams by the enzyme. We found that the outer membrane of E. cloacae strain 55M indeed had permeability to cefazolin about 14-fold lower than that of Escherichia coli, and that the number of beta-lactamase molecules produced by this constitutive mutant was exceptionally large (2 X 10(5) per cell). These conditions are expected to produce a low degree of resistance, but could not explain the high resistance level of the mutant. We showed that the beta-lactamase of this strain hydrolyzed third-generation beta-lactams at measurable rates. Although the V max for these compounds was less than 0.01% of that for cefazolin, the enzyme could hydrolyze them at rates comparable to the rate for cefazolin when the substrate concentration was near 0.1 microM, a concentration thought to be physiologically relevant for the inhibition of cell growth, because of the exceptionally high affinity of the enzyme to many third-generation compounds. Calculations based on kinetic parameters of the enzyme, outer membrane permeability, and affinity toward penicillin-binding proteins succeeded in predicting the MICs for several third-generation beta-lactams. The data suggest that hydrolysis may be more important than nonhydrolytic binding for the expression of the resistant phenotype, and that studies on the susceptibility of beta-lactams to beta-lactamases should be carried out at physiologically relevant, very low concentrations of the drug, rather than the customary very high concentrations, such as 100 microM.
Antimicrobial activity of HR810 against 419 strict anaerobic bacteria
Authors: Jones R N , Gerlach E H
Published: June 2012

HR810 and four other new beta-lactams were tested against 419 recent clinical anaerobic bacterial isolates. HR810 was found to have an antimicrobial spectrum most similar to that of cefotaxime, inhibiting 52.6% of Bacteroides fragilis group strains and 97.2% of all other anaerobic strains at an MIC of less than or equal to 16 micrograms/ml. Cefoxitin was found to have a narrower antimicrobial spectrum against the gram-positive anaerobic bacteria (8.4 to 10.1% less) than HR810 and cefotaxime, respectively.
Interaction of Epstein-Barr virus DNA polymerase and 5'-triphosphates of several antiviral nucleoside analogs
Authors: Chiou J F , Cheng Y C
Published: June 2012

The 5'-triphosphates of 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methyluracil, 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine, 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methylcytosine, 9-[(2-hydroxyethoxy)methyl]guanine, and 9-(1,3-dihydroxy-2-propoxymethyl)guanine had lower Ki values for Epstein-Barr virus DNA polymerase than has been reported elsewhere for host DNA polymerase. Inhibition of DNA elongation by these analogs ranged from moderate to strong, suggesting that preferential incorporation of these analogs into DNA by virus DNA polymerase may contribute to antiviral selectivity.
Norfloxacin versus trimethoprim-sulfamethoxazole in the therapy of uncomplicated, community-acquired urinary tract infections
Authors: Goldstein E J , Alpert M L , Ginsberg B P
Published: June 2012

In a prospective, randomized trial, norfloxacin (400 mg perorally, twice a day) was compared with trimethoprim-sulfamethoxazole (160-800 mg perorally, twice a day) in 45 patients with uncomplicated urinary tract infections. Escherichia coli was the most common isolate. Infections due to Enterobacter spp., Proteus mirabilis, Pseudomonas spp., and Staphylococcus spp. were also treated. Norfloxacin was equivalent in effectiveness and safety to trimethoprim-sulfamethoxazole, with a cure rate of 91% at the 5- to 9-day posttherapy visit and 88% at the 4- to 6-week posttherapy visit. It was well tolerated and had a low incidence of side effects.
Evidence for a disseminated erythromycin resistance determinant mediated by Tn917-like sequences among group D streptococci isolated from pigs, chickens, and humans
Authors: Rollins L D , Lee L N , LeBlanc D J
Published: June 2012

A total of 199 streptococci isolated from feces of healthy chickens, pigs, and beef cattle and 26 human clinical isolates were tested for resistance to kanamycin, streptomycin, tetracycline, erythromycin, and lincomycin. Of 66 isolates resistant to these antibiotics, 12 transferred one or more resistance traits by conjugation in broth. Erythromycin resistance (Emr) was transferred from 10 of the 12 successful donors. AvaI digests of plasmids isolated from Emr transconjugants derived from two human, two chicken, and one pig isolate contained three fragments similar in size to those produced from Tn3871, an Emr transposon. The three fragments from each of the five digests on Southern blots hybridized to radiolabeled Tn3871. Plasmid DNA from a transconjugant derived from a second pig isolate contained two of the three Tn3871-associated AvaI fragments. One of the AvaI fragments from each of the six plasmids hybridized with a radiolabeled probe containing a cloned AvaI fragment from Tn3871 that contained the Emr determinant. Transposition of the Emr trait was demonstrated for the plasmids derived from one human and one pig isolate. We concluded that extensive DNA homology existed between plasmids from streptococcal strains obtained from two human patients, two chickens, and two pigs and the Emr transposon Tn3871, which is very similar or identical to the well-characterized Emr transposon Tn917. The detection of Tn3871-like sequences in streptococcal isolates from Arkansas, Illinois, North Carolina, and Washington, D.C. indicates wide dissemination of Emr mediated by the same or closely related transposons.
Effects of changes in pH, medium, and inoculum size on the in vitro activity of amifloxacin against urinary isolates of Staphylococcus saprophyticus and Escherichia coli
Authors: Iravani A , Welty G S , Newton B R , Richard G A
Published: June 2012

The in vitro activity of amifloxacin (WIN 49375), a new fluoroquinolone, was compared with the activities of antimicrobial agents that are commonly used for the treatment of urinary tract infection (cinoxacin, cephalexin, gentamicin, amoxicillin, trimethoprim, and trimethoprim-sulfamethoxazole) against 25 strains of Staphylococcus saprophyticus and 28 strains of Escherichia coli. Bacterial strains were isolated from urine specimens of college women with acute urinary tract infections. Bacterial isolates were more susceptible to trimethoprim-sulfamethoxazole, trimethoprim, and amifloxacin than to the other drugs tested. The in vitro activity of amifloxacin against S. saprophyticus had an inverse relation to increases in the pH of the test medium. Changes in the type of culture medium had no effect on the in vitro activity of amifloxacin. There was a direct relationship between increases in inoculum size and the MICs of amifloxacin.
Selective inhibition of the accumulation of extracellular proteases of Pseudomonas aeruginosa by gentamicin and tobramycin
Authors: Warren R L , Baker N R , Johnson J , Stapleton M J
Published: June 2012

Gentamicin and tobramycin inhibited the accumulation of extracellular proteases secreted by Pseudomonas aeruginosa. The secretion of protease was inhibited at concentrations of these drugs that were below the level required to inhibit general protein synthesis. Neither magnesium ions nor high ionic strength antagonized the ability of the aminoglycosides to block secretion of the proteases. Under these culture conditions magnesium ions were shown to antagonize the effects of the aminoglycosides on protein synthesis and aminoglycoside-mediated lysozyme lysis of P. aeruginosa. These results suggested that the drugs blocked secretion of the proteases by acting at the level of the outer membrane.
In vitro and in vivo activities of DN-9550, a new broad-spectrum cephalosporin
Authors: Une T , Otani T , Sato M , Ikeuchi T , Osada Y , Ogawa H , Sato K , Mitsuhashi S
Published: June 2012

DN-9550 [(6R, 7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1H-imidazol-4-yl) methoxyiminoacetamido]-3-[(1-pyridinio)methyl]-8-oxo-5-thia -1-azabicyclo methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate hydrochloride] is a new semisynthetic cephalosporin with a broad spectrum of antibacterial activity against gram-positive and gram-negative bacteria. The activity of DN-9550 against most species of the family Enterobacteriaceae was roughly comparable to that of ceftazidime, slightly lower than that of cefotaxime, and far exceeded that of cefoperazone. Against Citrobacter freundii, Enterobacter cloacae, and Serratia marcescens, DN-9550 was more active than ceftazidime and cefotaxime. DN-9550 and ceftazidime were significantly more active than cefotaxime against Pseudomonas aeruginosa, but DN-9550 and cefotaxime were clearly more active than ceftazidime against staphylococci and streptococci. Haemophilus influenzae and Neisseria gonorrhoeae were also highly susceptible to DN-9550, but Bacteroides fragilis was generally not susceptible to the compound. DN-9550 was stable to various types of beta-lactamases and had high affinities for penicillin-binding protein 3 of both Escherichia coli and P. aeruginosa. When DN-9550 was administered subcutaneously to mice experimentally infected with Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, or Pseudomonas aeruginosa, its efficacy well reflected its in vitro potency.
Intraoperative ceforanide pharmacokinetics and protein binding
Authors: DiPiro J T , Bayoumi S M , Vallner J J , Nesbit R R , Gokhale R , Rissing J P
Published: June 2012

The pharmacokinetics and protein binding of ceforanide were studied in 15 patients undergoing cholecystectomies. Each patient received ceforanide (20 mg/kg) intravenously on arrival in the operating room, after which serial blood samples were collected during the elimination phase for determination of total and free ceforanide concentrations in the serum. A high-pressure liquid chromatography assay was used, with a centrifugal filtration system for free-drug determinations. Serum concentration data for each individual were subjected to linear regression to determine the elimination rate constants (total and free drug), volumes of distribution, and systemic clearances. The mean elimination rate constants were 0.41 and 0.50 h-1 for total and free ceforanide, respectively. The mean percentage of ceforanide bound to serum protein was 87.9%. The relationship of the free ceforanide concentration to the total concentration appeared to be linear. The data were fit to double-reciprocal and half-reciprocal relationships with good agreement, showing one binding site and an association constant range of 1.6 X 10(7) to 1.9 X 10(7) at these in vivo concentrations. The mean volume of distribution and mean systemic clearance of total drug were 100 ml/kg and 45.9 ml/min per 1.73 m2, respectively. Ceforanide consistently produced higher intraoperative total drug concentrations compared with those of cefazolin and cefoxitin from similar studies.
In vitro susceptibilities of isolates from patients with Branhamella catarrhalis pneumonia compared with those of colonizing strains
Authors: Sweeney K G , Verghese A , Needham C A
Published: June 2012

Branhamella catarrhalis has recently been recognized as an opportunistic respiratory pathogen. We tested 10 isolates recovered from patients with documented B. catarrhalis pneumonia and 15 colonizing isolates for their susceptibility to 19 antimicrobial agents and for their ability to produce beta-lactamase. Eight of ten disease isolates and 12 of 15 colonizing isolates produced a detectable beta-lactamase. The isolates that were negative for beta-lactamase were susceptible to all agents tested, including penicillin G. Although all strains were found to be susceptible to the majority of the newer agents by broth dilution testing, the most active new semisynthetic penicillin was azlocillin (MIC that inhibited 90% of strains, 0.5 micrograms/ml), and moxalactam had the greatest potency among the cephalosporins (MIC that inhibited 90% of strains, 0.06 micrograms/ml). Members of the first- and second-generation cephalosporins had only moderate activity. All disease isolates were susceptible to the aminoglycosides and to trimethoprim-sulfamethoxazole and resistant to vancomycin. The antibiotic susceptibilities of the disease isolates were not different from those of the colonizing strains. The results of standardized disk diffusion testing did not correlate well with those of dilution testing for penicillin or ampicillin. However, disk diffusion testing did predict susceptibility adequately for the remainder of the antibiotics tested.
In vitro activity of BMY-28142 in comparison with those of other beta-lactam antimicrobial agents
Authors: Tsuji A , Maniatis A , Bertram M A , Young L S
Published: June 2012

The in vitro susceptibility of 406 clinical isolates to BMY-28142, a new semisynthetic cephem, was evaluated and compared with cefpimizole, HR 810, ceftazidime, cefotaxime, moxalactam, and cefoperazone in a broth microdilution assay. On a weight basis, the activity of BMY-28142 against Escherichia coli, Proteus species, and Klebsiella-Enterobacter-Serratia was superior to the other cephems. Against gentamicin-susceptible and -resistant Pseudomonas aeruginosa, BMY-28142 was more active than the other cephems, except ceftazidime and HR 810. A total of 74% of gram-negative and 56% of gram-positive isolates resistant to third-generation cephalosporins were susceptible to less than or equal to 8 micrograms of BMY-28142 per ml. Finally, for 83% of tested isolates, the bactericidal concentration of BMY-28142 was within one dilution of the inhibitory concentration.
Inhibition of the rate of 14CO2 production from [14C]ethanol in rats given beta-lactam antibiotics with disulfiram-like effects
Authors: Turcan R G , MacDonald C M , Ings R M , Coombes J D
Published: June 2012

An animal model has been developed to investigate the potentials of various beta-lactam antibiotics for inducing (or producing) disulfiram-like effects. The method, which measures the rate of 14CO2 production in rats after [14C]ethanol administration, is simple to operate and sensitive. On the basis of available clinical information the model appears to be highly predictive for the likely incidence of disulfiram-like side effects in humans. Rats were pretreated intravenously with beta-lactam antibiotics (420 or 500 mg/kg-1) 18 h before ethanol administration or with N-methyl tetrazole thiol (NMTT; 1-methyl-5-mercaptotetrazole) at 96 mg kg-1, 6 h before ethanol administration. The rate of 14CO2 production was decreased to 70 to 80% of control levels by NMTT and the NMTT-containing beta-lactam antibiotics moxalactam, cefamandole, and cefoperazone. Cefotaxime, cephalothin, and cefuroxime which do not contain the NMTT side chain had no significant effect on 14CO2 production. Oral administration of moxalactam (500 mg kg-1) and NMTT (96 mg kg-1) 18 and 6 h, respectively, before ethanol administration significantly decreased 14CO2 production. Intravenous administration of moxalactam (500 mg kg-1) to rats with cannulated bile ducts 18 h before ethanol administration had no statistically significant effect on 14CO2 production, although the rate of 14CO2 production was decreased to 89% of the control level. The effect of dose level and dose interval was also investigated by using moxalactam. The results obtained support the hypothesis that disulfiram-like side effects associated with beta-lactam antibiotics are mediated by NMTT which is released and reabsorbed from the gut after biliary elimination of the parent beta-lactam antibiotic. The time course of inhibition of ethanol metabolism by moxalactam appears to differ from that of disulfiram.
Morphological changes induced by beta-lactam antibiotics in Mycobacterium avium-intracellulare complex
Authors: Mizuguchi Y , Ogawa M , Udou T
Published: June 2012

In vitro activity of seven beta-lactam antibiotics against strains of Mycobacterium avium-intracellulare was evaluated by the agar dilution method. The activity was influenced by the presence or absence of Tween 80 in Dubos medium, and cephazolin and cefotaxime were effective against most strains in the presence of Tween 80. beta-Lactam antibiotics at low concentrations induced long filamentous cells with branching. In contrast to the filaments induced by ampicillin, in which septation was rarely observed, filaments induced by cephazolin had many septa, suggesting that the mechanisms of filament induction were different from the drugs used. At high concentrations, ampicillin and cephazolin induced osmotically sensitive cells with bulging at polar end of the cells. Analysis of penicillin binding proteins (PBPs) of the organism showed that there were at least nine PBPs with molecular weights between 32,000 and 94,000 in the cytoplasmic membrane. Ampicillin showed the highest affinity for PBPs 1a or 1b, or both, and also PBPs 3a or 3b, or both. In contrast, there was very little specificity of binding of cephazolin for any of the PBPs.
In vitro susceptibility of Neisseria gonorrhoeae to 2-acetylpyridine thiosemicarbazones
Authors: Christenson B , Rodríguez J R , Gorbea H F , Ramírez-Rond C H
Published: June 2012

MICs of 20 2-acetylpyridine thiosemicarbazones and penicillin were determined for 25 clinical isolates of beta-lactamase-positive and beta-lactamase-negative Neisseria gonorrhoeae strains. The compounds most active against the beta-lactamase-producing strains were the N4,N4-disubstituted derivatives and the thiosemicarbazone derivatives of the 2-acetylpyridines, followed by the other compounds related to the 2-acetylpyridine thiosemicarbazones.
Vancomycin disposition during continuous ambulatory peritoneal dialysis: a pharmacokinetic analysis of peritoneal drug transport
Authors: Rogge M C , Johnson C A , Zimmerman S W , Welling P G
Published: June 2012

Expressions are presented to describe the absorption and also clearance of drugs administered into the peritoneal cavity of patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Application of the expressions to vancomycin kinetics in five male CAPD patients showed that therapeutic levels of vancomycin can readily be achieved and maintained in the systemic circulation by administering the appropriate loading and maintenance doses. The intrinsic peritoneal clearance of vancomycin reported here is higher than the apparent clearances reported previously, averaging 300 to 500 ml/min under the conditions used in this study. The low apparent clearances previously reported are useful clinically although they do not represent the true efficiency of vancomycin removal by CAPD. The degree to which apparent clearance underestimates the true intrinsic clearance is exponentially related to the dwell time of dialysate in the peritoneum. Intraperitoneal administration is a practical alternative to other routes for CAPD patients needing antibiotic or other therapy.
Purification and properties of inducible penicillin beta-lactamase isolated from Alcaligenes faecalis
Authors: Fujii T , Sato K , Inoue M , Mitsuhashi S
Published: June 2012

An inducible penicillin beta-lactamase was purified from a strain of Alcaligenes faecalis resistant to beta-lactam antibiotics. The purified enzyme preparation gave a single protein band on polyacrylamide gel electrophoresis, and its molecular weight was 29,000 based on sodium dodecyl sulfate-acrylamide gel electrophoresis. Its isoelectric point was 5.9. The enzyme more rapidly hydrolyzed penicillins, such as penicillin G, ampicillin, carbenicillin, piperacillin, and cloxacillin, than it hydrolyzed cephalosporins. For the hydrolysis of penicillin G, the optimal pH was 5.5, and the optimal temperature was 35 degrees C. The enzyme activity was inhibited by iodine, Cu2+, Hg2+, and EDTA but was not inhibited by clavulanic acid and sulbactam.
Tobramycin resistance of Pseudomonas aeruginosa cells growing as a biofilm on urinary catheter material
Authors: Nickel J C , Ruseska I , Wright J B , Costerton J W
Published: June 2012

When disks of urinary catheter material were exposed to the flow of artificial urine containing cells of Pseudomonas aeruginosa, a thick adherent biofilm, composed of these bacteria and of their exopolysaccharide products, developed on the latex surface within 8 h. After this colonization, sterile artificial urine containing 1,000 micrograms of tobramycin per ml was flowed past this established biofilm, and a significant proportion of the bacterial cells within the biofilm were found to be still viable after 12 h of exposure to this very high concentration of aminoglycoside antibiotic. Planktonic (floating) cells taken from the test system just before the exposure of the biofilm to the antibiotic were completely killed by 50 micrograms of tobramycin per ml. The MIC of tobramycin for cells taken from the seeding cultures before colonization of the catheter material, and for surviving cells recovered directly from the tobramycin-treated biofilm, was found to be 0.4 micrograms/ml when dispersed cells were assayed by standard methods. These data indicate that growth within thick adherent biofilms confers a measure of tobramycin resistance on cells of P. aeruginosa.
Comparative in vitro activities of selected antimicrobial agents against Aeromonas species and Plesiomonas shigelloides
Authors: Reinhardt J F , George W L
Published: June 2012

The in vitro antimicrobial susceptibilities of fecal isolates of Aeromonas caviae, Aeromonas hydrophila, Aeromonas sobria, and Plesiomonas shigelloides were tested by agar dilution. This in vitro study suggested that ciprofloxacin, enoxacin, norfloxacin, tetracycline, and trimethoprim-sulfamethoxazole might be effective oral agents for treatment of diarrhea involving Aeromonas spp. or P. shigelloides.