bluuebunny/crossref_metadata_2025 huggingface dataset:
Moxalactam and cefazolin: comparative pharmacokinetics in normal subjects
Authors: Scheld W M , Spyker D A , Donowitz G R , Bolton W K , Sande M A
Published: June 2012

Moxalactam, a new beta-lactam antibiotic with a wide in vitro spectrum of activity, was compared with cefazolin after intravenous and intramuscular administration of 1.0 g in a double-blind crossover design in 21 adult male subjects with normal renal function. Serum samples were obtained at 0.5, 1, 2, 3, 4, 6, 8, and 12 h, and urine was collected at 0 to 2, 2 to 4, 4 to 6, 6 to 8, and 8 to 12 h after dosing. Intravenous kinetics were described by a linear two-compartment model. For moxalactam, the drug clearance and volume of distribution were larger (115.2 versus 75.9 ml/min per 70 kg, P = 0.001, and 0.44 versus 0.19 liter/kg, P less than 0.001, respectively), and the t1/2beta was longer (3.47 versus 2.18 h, P = 0.01), with correspondingly smaller area under the curve (151 versus 236 h x mg/ml, P = 0.003) and lower serum concentration at 30 min (62 versus 106 micrograms/ml, P = 0.003) than cefazolin. Intramuscular kinetics were similar and were well described by a single-compartment model. Urinary recovery was essentially identical for both drugs: 55 to 75% in 8 h. Consistent departures from the two-compartment model for moxalactam (not noted for cefazolin) suggested enterohepatic recirculation of moxalactam. Both drugs were well tolerated, and no adverse reactions were noted.
Latex agglutination inhibition card test for gentamicin assay: clinical evaluation and comparison with radioimmunoassay and bioassay
Authors: Standiford H C , Bernstein D , Nipper H C , Caplan E , Tatem B , Hall J S , Reynolds J
Published: June 2012

Gentamicin levels were determined in 100 serum specimens by a new latex agglutination inhibition card test, a radioimmunoassay (RIA), and a bioassay. Correlation coefficients determined by linear regression analysis demonstrated that the levels obtained by the latex agglutination inhibition card test had a high degree of correlation with the RIA and could be performed much faster and more economically when processing small numbers of specimens. The bioassay had a slightly lower degree of correlation with both the RIA and the latex test and was adversely influenced by concurrently administered antibiotics which could not be eliminated by beta-lactamase. When measuring gentamicin concentrations above 2 micrograms/ml, the coefficient of variation was less than 14% for the latex agglutination assay compared with 15% for the bioassay and 12% for RIA. The latex agglutination inhibition card test is a rapid, accurate, specific, and reproducible method for monitoring gentamicin levels in patients and is particularly applicable for laboratories processing small numbers of specimens.
In vitro and in vivo antibacterial effects of combinations of beta-lactam antibiotics
Authors: Kuck N A , Testa R T , Forbes M
Published: June 2012

The effects of combining the new broad-spectrum penicillins piperacillin and mezlocillin with cefoxitin, cefamandole, or cephalothin on the antibacterial activities of these antibodies were determined in vitro against 50 to 109 bacterial strains and in six experimental infections in mice. Against strains of Escherichia coli, Klebsiella, Proteus mirabilis, Salmonella, Acinetobacter, Enterococcus, and Staphylococcus, the combinations exhibited synergistic, indifferent, or additive effects, but no antagonism. Against strains of four groups of organisms (Pseudomonas, Serratia, Enterobacter, and indole-positive Proteus), a high incidence of antagonism was observed, particularly with combinations containing cefoxitin (60 to 100%). The penicillins were antagonized by the cephalosporin antibiotics. In vitro effects were reflected in vivo. Mice infected with cultures associated with synergistic or additive in vitro effects were protected with lower doses of piperacillin when this antibiotic was administered with ineffective doses of cefoxitin than when piperacillin was used alone. Infections with cultures associated with in vitro antagonism required two- to eightfold higher doses of piperacillin and mezlocillin when these antibiotics were used in combination with the cephalosporins. The clinical implications of these effects should be considered.
Clinical pharmacology of moxalactam in patients with malignant disease
Authors: Estey E H , Weaver S S , Ho D H , Bodey G P
Published: June 2012

Pharmacological studies of moxalactam were conducted with 37 cancer patients. Intramuscular administration of 500 mg of moxalactam to 10 patients produced a mean peak serum concentration of 12.4 micrograms/ml. The serum terminal-phase half-life was 3.9 h. Intravenous administration of 500 mg of moxalactam over 5 min to the same 10 patients produced a mean serum concentration of 42.0 micrograms/ml at 15 min, which decreased to 3.3 micrograms/ml at 6 h. A dose of 1 g of moxalactam was given in an identical manner to the same 10 patients. The mean serum concentration was 69.7 micrograms/ml at 15 min and 7.4 micrograms/ml at 6 h. The mean proportions of a drug recovered in the urine by 12 h after administration were 59% after the intramuscular dose and 61 and 55% after the single intravenous doses. Multiple-dose intravenous studies were also conducted. The serum terminal-phase half-life varied from 2.0 to 3.2 h. Continuous infusion studies were performed by up to 9 days by using a loading dose of 1 g over 0.5 h, followed by 2 g every 6 h. Serum concentrations were maintained at about 30.0 micrograms/ml during the study period.
Inhibition of respiratory syncytial virus-host cell interactions by mono- and diamidines
Authors: Dubovi E J , Geratz J D , Shaver S R , Tidwell R R
Published: June 2012

Several aromatic mono- and diamidines were found to block cell fusion induced by respiratory syncytial virus. The best inhibitors were able to achieve complete suppression of syncytium formation at a concentration of 1.0 microM. Inhibition occurred in respiratory syncytial virus-infected HEp-2 and CV-1 cells, but the same inhibitors were ineffective in preventing fusion induced by parainfluenza virus type 3. The fusion inhibitors did not reduce single-cycle virus yields, but did reduce multiple-cycle yields. In addition, the active compounds caused a significant retardation of respiratory syncytial virus penetration. The mechanism by which amidines interfere with respiratory syncytial virus-host cell interactions is unknown, but parallels can be drawn between antiviral activity and the ability of the compounds to inhibit certain trypsin-like proteases.
Effects of Halo Analogs of Glycerol 3-Phosphate and Dihydroxyacetone Phosphate upon
Escherichia coli
Authors: Mildener Barry , Fondy Thomas P. , Engel Robert , Tropp Burton E.
Published: June 2012

The fluoro and chloro analogs of glycerol 3-phosphate inhibit the growth of
Escherichia coli
and affect bacterial enzymes involved in lipid synthesis.
Moxalactam therapy for a wide spectrum of bacterial infections in adults
Authors: Tofte R W , Rotschafer J , Solliday J , Crossley K B
Published: June 2012

We evaluated the efficacy and toxicity of moxalactam during treatment of 45 documented infections in 36 patients. A majority of patients received 4.5 g of moxalactam per day. There was a good clinical response in 42 of the 45 (94%) infections, including 3 bacteremias, 20 skin and soft tissue infections, 6 gram-negative lower respiratory tract infections, 6 purulent diabetic foot ulcers, 3 wound infections, 3 urinary tract infections, and 4 miscellaneous infections (meningitis, suppurative phlebitis, peritonitis, bursitis). Previously, 11 of these patients had failed to respond to other antibiotics. Our three treatment failures were attributed to abnormal host defense in two patients and to a resistant enterococcal urinary tract infection in another. Moxalactam was tolerated well as produced minimal renal, hepatic, and hematological toxicities. The only serious adverse effect were the development of documented pseudomembranous colitis in one patient and progressive renal dysfunction in another. Acquisition of resistance among noneradicated isolates during therapy was not demonstrated.
Cefoperazone treatment of experimental endocarditis
Authors: Snepar R A , Carrizosa J , Kobasa W D , Kaye D
Published: June 2012

Cefoperazone (10 mg/kg) and cephalothin (20 mg/kg) administered intramuscularly every 6 h were both effective in reducing the number of Staphylococcus aureus cells in vegetations in rabbits with endocarditis. Cefoperazone produced higher peak concentrations and greater bactericidal activity in serum than did cephalothin. Cefoperazone (40 mg/kg) administered every 6 h was significantly more effective than cefamandole (40 mg/kg) administered every 6 h in reducing the number of Enterobacter aerogenes cells in vegetations. Although cefamandole produced higher peak concentrations in serum, the serum bactericidal activity was greater with cefoperazone. The half-lives in serum were 0.64 h for cefoperazone and 0.46 h for cephalothin and cefamandole.
Effect of subinhibitory concentrations of mecillinam on the serum susceptibility of Escherichia coli strains
Authors: Taylor P W , Gaunt H , Unger F M
Published: June 2012

For serum-resistant clinical isolates of Escherichia coli were grown in the presence of various subinhibitory concentrations of mecillinam or pivmecillinam and then exposed to the bactericidal action of human serum. All strains became more serum susceptible as a result of pregrowth in medium containing mecillinam, but the concentration of antibiotic needed to produce the effect varied according to the strain being used. Production of ovoid or round cells was a prerequisite for sensitization to serum. Growth in the presence of mecillinam did not alter the response to serum of a serum-susceptible E. coli strain.
Treatment of gonorrhea: comparison of cefotaxime and penicillin
Authors: Simpson M L , Khan M Y , Siddiqui Y , Gruninger R P , Wigren D I
Published: June 2012

Ninety-seven patients with 118 sites infected with Neisseria gonorrhoeae were treated with a single dose of either procaine penicillin G (4.8 x 10(6) U) or cefotoxime (1.0 g) intramuscularly. Only the penicillin group took 1 g of probenecid orally. The numbers of infected sites in each treatment group were as follows: penicillin-urethra, 37; rectum, 9; cervix, 8; and pharynx, 4; cefotaxime-urethra, 42; rectum, 9; cervix, 5; and pharynx, 4. The cure rates in each treatment group were 100%. No adverse reactions were noted in either group. beta-Lactamase-positive N. gonorrhoeae strains were not found. Ninety-five percent of clinical isolates were inhibited by less than or equal to 0.007 micrograms of cefotaxime and less than or equal to 0.25 micrograms of penicillin per ml. In this study cefotaxime was as effective as procaine penicillin in the treatment of uncomplicated gonorrhea.
Bacteriological aspects of selective decontamination of the digestive tract as a method of infection prevention in granulocytopenic patients
Authors: de Vries-Hospers H G , Sleijfer D T , Mulder N H , van der Waaij D , Neiweg H O , van Saene H K
Published: June 2012

We describe the bacteriological results of a controlled clinical trial of selective decontamination of the digestive tract as a method of infection prevention in granulocytopenic patients. Selective elimination of Enterobacteriaceae and Pseudomonadaceae species was accomplished by the oral administration of nalidixic acid, co-trimoxazole, or polymyxin. Yeasts were eliminated selectively by amphotericin B or nystatin treatment. The drugs used in this study were chosen because of their capacities to selectively eliminate gram-negative rods and yeast without affecting the anaerobic part of the gut flora which is responsible for colonization resistance. Compared with the control group, the selectively decontaminated patients had significantly fewer (P less than 0.0005) gram-negative rods or yeasts or both in their throat swab cultures and in their feces. This reduction may explain the clinical effectiveness of selective decontamination.
Treatment of uncomplicated urinary tract infections with trimethoprim versus sulfisoxazole, with special reference to antibody-coated bacteria and fecal flora
Authors: Iravani A , Richard G A , Baer H
Published: June 2012

A total of 331 college-age women with urinary tract infections were studied. These women were assigned randomly to the following groups: 50 patients treated with 400 mg of trimethoprim (TMP) per day for 14 days (designated the TMP400/14d group); 50 treated with 2.0 g of sulfisoxazole (SZ) per day for 14 days (SZ/14d group); 120 treated with 200 mg of TMP per day for 10 days (TMP200/10d group); and 111 treated with 2.0 g of SZ per day for 10 days (SZ/10d group). By the last day of therapy, clinical and bacteriological cure rates were 100% in the TMP400/14d, SZ/14d, and TMP200/10d groups and 97.1% in SZ/10d group. At 1 week after therapy ended, the initial urinary pathogens remained eradicated in 100% of the TMP400/14d group, 98.2% of the TMP200/10d group, 95.6% of the SZ/14d group, and 98.0% of the SZ/10d group at 4 weeks after therapy ended, the clinical cure rates were 92.0% in the TMP400/14d group, 92.0% in the SZ/14d group, 89.0% in the TMP200/10d group, and 90.0% in the SZ/10d group. At 4 and 24 weeks after therapy ended, the recurrence rates in the four treatment groups did not differ significantly. The antibody-coated bacteria test localized 39.5% of the infections to kidneys and 56.8% of the infections to bladders. Neither symptoms nor responses to therapy were correlated with the antibody-coated bacteria test results. Both TMP at a dose of 200 mg/day and SZ were tolerated well. TMP at a dose of 400 mg/day was associated with a skin rash in 24% of the patients receiving this therapy. TMP suppressed fecal Escherichia coli. SZ increased the number of sulfa-resistant fecal isolates; however, this phenomenon did not affect the rate of sulfa-resistant recurrences.
Anomalous cellular morphology and growth characteristics of Neisseria meningitidis in subminimal inhibitory concentrations of penicillin G
Authors: Neirinck L G , DeVoe I W
Published: June 2012

The effects of subminimal inhibitory concentrations of penicillin G on Neisseria meningitidis in the presence and absence of selected stabilizers were examined. Subminimal inhibitory concentrations of penicillin G decreased cell numbers and altered both colonial and ultrastructural morphologies of this meningococcus. Although these levels of penicillin did not have immediate adverse effects on cell mass increase, deoxyribonucleic acid synthesis, or the incorporation of [3H]leucine into protein, they did significantly alter the division rate and the integrity of the cell envelope. The inability of many of the abnormal membranous cell types produced in subminimal inhibitory concentrations of penicillin to form either complete or properly oriented division septa and the overproduction of cell wall material at such sites was indicative of the disruptive effects of this antibiotic on functions necessary for maintaining the normal division process. The addition of the stabilizers polyvinylpyrrolidone-40 and horse serum to the test medium diminished the effects of penicillin G as evidenced by a fourfold increase in the minimal inhibitory concentration. Moreover, such stabilizers maintained the association of the outer membrane with the peptidoglycan and inner membrane.
Inactivation of mycoplasmas by long-chain alcohols
Authors: Fletcher R D , Gilbertson J R , Albers A C , White J D
Published: June 2012

In this report, we describe the inhibitory activity of long-chain alcohols on the growth of Mycoplasma gallisepticum and Mycoplasma pneumoniae. Peak inhibition was recorded with saturated primary alcohols (64 microM) varying in chain length from 16 to 19 carbon atoms. The unsaturated alcohols (oleyl, linoleyl, and linolenyl) and the secondary alcohol (pentadecan-2-ol), when employed in the same test conditions, were considerably less effective growth inhibitors than the primary saturated alcohols. Stearic and palmitic acids were also ineffective as growth inhibitors of M. pneumoniae and M. gallisepticum at a 128 microM concentration. Because these antimycoplasma agents are fatty alcohols and cholesterol is known to be required for the growth of some mycoplasmas, additional cholesterol was added in an attempt to reverse the inhibition observed with these agents. Cholesterol at a 128 microM concentration did not significantly relieve the growth inhibition observed with stearyl alcohol at a 48 microM concentration. Mammalian cell cultures were found to be significantly more resistant to the effects of these inhibitory alcohols than were the mycoplasmas. Electron micrographs showed that inclusion of stearyl alcohol in the culture medium produced changes in the cellular morphology of the treated mycoplasmas.
Combined protective effects on interferon and interferon induction on herpes simplex and ectromelia virus infections in mice
Authors: Imanishi J , Matsubara M , Won C J , Nomura H , Kishida T
Published: June 2012

Mouse interferon or the induction of mouse interferon with polyriboinosinic acid-polyribocytidylic acid significantly protected mice against herpes simplex and ectromelia viral infections. When polyriboinosinic acid-polyribocytidylic acid was administered 24 h before herpes simplex or ectromelia viral infection and mouse interferon was administered shortly before and 24 h after infection, a combined protective effect against either herpes simplex or ectromelia viral infection in mice was evident. There was a significant decrease in the mortality rate with the combined treatment as compared either with the rate in group treated with interferon or polyriboinosinic acid-polyribocytidylic acid.
Effect of Acyclovir on Latent Herpes Simplex Virus Infections in Trigeminal Ganglia of Mice
Authors: Klein Richard J. , DeStefano Eugene , Friedman-kien Alvin E. , Brady Eileen
Published: June 2012

The inhibition by acyclovir of the in vitro reactivation of herpes simplex virus from latently infected ganglion explant cultures is dependent on the continuous presence of this drug. Administration of acyclovir subcutaneously, orally, or by continuous perfusion to mice with established latent infections did not eliminate latent virus from the trigeminal ganglia.
Pharmacokinetics of cefoperazone in patients with neoplastic disease
Authors: Maksymiuk A W , LeBlanc B M , Brown N S , Ho D H , Bodey G P
Published: June 2012

The pharmacokinetics of cefoperazone, a new semisynthetic cephalosporin, were studied in 34 patients with neoplastic disease. This compound was administered in a variety of doses and schedules without observable toxicity in any patient. The mean peak serum concentration after a 15-min intravenous infusion of 2 g was 264 microgram/ml after the first dose; the serum half-life was 2.1 h. There was no significant change in half-life or serum concentrations after 4 or 7 days of therapy. The mean peak serum concentration after infusion of 1 g over 15 min was 133 microgram/ml, with a mean of 10.7 microgram/ml at 6 h. The serum half-life was 2 h. The mean peak serum concentration after infusion of 1 g over 0.5 h was 101 microgram/ml. When 8 g was subsequently administered daily by a continuous infusion schedule, levels were maintained at 80 microgram/ml. When the dose was increased to 16 g daily, serum concentrations were maintained at an average of 153 microgram/ml. Only 37% of cefoperazone was recovered in the urine in a 12-h period after the initial dose, suggesting the importance of other mechanisms of excretion; however, serum concentrations in one patient with renal insufficiency were significantly higher than serum concentrations in patients with normal renal function.
Importance of bacterial growth phase in determining minimal bactericidal concentrations of penicillin and methicillin
Authors: Kim K S , Anthony B F
Published: June 2012

The minimal inhibitory concentrations of penicillin against 96 strains of group B streptococci and of methicillin against 10 strains of Staphylococcus aureus were unrelated to the growth phase of test bacteria. However, the minimal bactericidal concentrations were significantly higher in the stationary phase than the logarithmic phase for both organisms (P less than 0.001 and less than 0.05, respectively).
Segregation of 5-Fluorocytosine-Resistant Variants by
Candida albicans
Authors: Whelan William L. , Beneke Everett S. , Rogers Alvin L. , Soll David R.
Published: June 2012

Spontaneous production of 5-fluorocytosine-resistant variants by three
Candida albicans
isolates is due to segregation from a preexisting heterozygous state.
Synergism in the Inhibition of
Bacillus subtilis
by Combinations of Lipophilic Weak Acids and Fatty Alcohols
Authors: Corner Thomas R.
Published: June 2012

Combinations of two lipophilic weak acids and alcohols acted synergistically to inhibit growth of
Bacillus subtilis
. Alcohols contributed to both reversible and irreversible inhibitions by acids.
Comparative pharmacokinetics of cyclacillin and amoxicillin in infants and children
Authors: Ginsburg C M , McCracken G H , Zweighaft T C , Clahsen J C
Published: June 2012

Concentrations of cyclacillin in serum over a 6-h period were similar in fasted and milk-fed infants who received 25-mg/kg doses of cyclacillin suspension. Measured by the concentration in serum after oral administration of 15-mg/kg doses, cyclacillin was absorbed more rapidly, reached larger concentrations, and was cleared more promptly than was amoxicillin.
Isolation of cairomycins A and C
Authors: Shimi I R , Fathey S
Published: June 2012

Cairomycin B in the fermentation broths of Streptomyces sp. strain AS-C-19 accompanied cairomycin A and cairomycin C. The cairomycins are peptides with potent activity against gram-positive bacteria. On acid hydrolysis, cairomycin A yielded valine and aspartic acid, whereas cairomycin C yielded lysine, glycine, valine, leucine, and aspartic acid, as identified by paper and gas chromatography. These amino acids were found to exist in their alpha-L form. Cairomycin A was tentatively assigned a 6-isopropyl-2,5-diketopiperazine-3-acetic acid structure. The three cairomycins were distinct from each other in their ultraviolet, infrared, and mass spectra; elemental analyses; and their chromatographic behavior in different developing solvents.
Aminoglycoside-resistant mutants of Pseudomonas aeruginosa deficient in cytochrome d, nitrite reductase, and aerobic transport
Authors: Bryan L E , Kwan S
Published: June 2012

Two gentamicin-resistant mutants of Pseudomonas aeruginosa PAO 503 were selected after ethyl methane sulfonate mutagenesis. Mutant PAO 2403 had significantly increased resistance to aminoglycoside but not to other antibiotics. Mutant PAO 2402 showed a similar spectrum of resistance but of lower magnitude. Both mutants showed no detectable cytochrome d and had a high frequency of reversion to a fully wild-type phenotype. PAO 2403 had a marked decrease and PAO 2402 had a moderate decrease in nitrite reductase activity. Both mutants had reduced uptake of gentamicin and dihydrostreptomycin. Mutant PAO 2403 showed a general decrease in transport rate of cationic compounds, whereas mutant PAO 2402 had only deficient glucose transport. Both mutants showed enhanced rates of glutamine transport and no change in glutamic acid transport. Other components of electron transport and oxidative phosphorylation were normal. These mutants involve ferrocytochrome C551 oxidoreductase formed only on anaerobic growth but illustrate transport defects in aerobically grown cells.
Effects of Low Penicillin Concentrations on Cell Morphology and on Peptidoglycan and Protein Synthesis in a Tolerant
Streptococcus
Strain
Authors: Mychajlonka Myron
Published: June 2012

Rates of protein and peptidoglycan synthesis were determined by pulse-labeling techniques before and after treatment of exponentially growing cultures of
Streptococcus mutans
FA-1 with a number of concentrations of penicillin G (0.05, 0.1, 0.3, and 0.4 μg/ml). These penicillin concentrations were all less than that required to saturate the specific penicillin-binding sites present on the surface of this organism (0.5 μg/ml), but were all greater than and, in fact, were multiples of the minimum inhibitory concentration (0.02 μg/ml). Low concentrations of penicillin G (2.5× the minimum inhibitory concentration) immediately halted the exponential increase in the rate of peptidoglycan synthesis normally expected as the result of cell multiplication, but allowed the rate of peptidoglycan synthesis occurring at the time of penicillin addition to be maintained for almost 1 h. An increased penicillin concentration (5× the minimum inhibitory concentration) allowed the rate of peptidoglycan synthesis occurring at the time of penicillin addition to be maintained for a shorter length of time (~0.67 h). Still greater penicillin concentrations caused an immediate inhibition of the peptidoglycan synthetic rate. The effect of penicillin on the rate of protein synthesis was similar, although less pronounced. Samples were taken for scanning electron microscopy immediately before and after 3 h of treatment with a low (2.5× the minimum inhibitory concentration) concentration of penicillin. The surface areas and volumes of the cells in these samples were calculated from the electron micrographs by using computer reconstruction techniques. From the frequency distributions of surface area, the plots of surface area to volume ratio as a function of surface area, and the pulse-labeling data mentioned previously, low, growth-inhibitory concentrations (2.5× the minimum inhibitory concentration) of penicillin are proposed (i) to inhibit the constriction of the division septum, (ii) to prevent the establishment or maturation of new envelope growth sites, and (iii) to have no immediate effects on the synthesis of cell wall peptidoglycan already in progress at the time of penicillin addition.
Experimental endocarditis caused by Streptococcus sanguis: single and combined antibiotic therapy
Authors: Vicente M V , Olay T , Rodríguez A
Published: June 2012

The effectiveness of penicillin G, fosfomycin, and cefoxitin alone and in combination was studied in vitro and in the treatment of left-sided Streptococcus sanguis endocarditis in rabbits. In vitro, the combinations penicillin G plus fosfomycin, penicillin G plus cefoxitin, and fosfomycin plus cefoxitin were synergistic or partially synergistic for S sanguis. Therapy with the combinations was more effective in eradicating the species from cardiac vegetations that was that with each antibiotic used alone.
Lactobacillus prophylaxis for diarrhea due to enterotoxigenic Escherichia coli
Authors: Clements M L , Levine M M , Black R E , Robins-Browne R M , Cisneros L A , Drusano G L , Lanata C F , Saah A J
Published: June 2012

In vitro and animal experiments indicated that lactobacilli might prevent Escherichia coli from colonizing the intestine and may produce substances counteracting enterotoxin. Lactinex, a commercial preparation of dried Lactobacillus acidophilus and L. bulgaricus, is marketed for uncomplicated diarrhea. Preliminary experiments in nonfasting volunteers indicated that lactobacilli in this preparation colonized the small intestine for up to 6 h. To evaluate the protective efficacy of Lactinex, a double-blind randomized study was carried out in which 48 volunteers (23 receiving Lactinex and 25 receiving placebos) were challenged with E. coli strains that produced heat-stable or heat-labile enterotoxins or both. No significant differences between the two groups were noted with respect to attack rate, incubation period, duration of diarrhea, volume and number of liquid stools, and coproculture yields. These data suggest that this lactobacillus preparations does not prevent or alter the course of enterotoxigenic E. coli diarrhea in adults. Lack of efficacy occurred despite efforts to maximize small bowel colonization, including administration of Lactinex in milk and in a 6-hour-interval regimen during 36 h before and 96 h after challenge.
In Vitro Comparison of
N
-Formimidoyl Thienamycin, Piperacillin, Cefotaxime, and Cefoperazone
Authors: Tutlane Victoria A. , Mccloskey Richard V. , Trent Judith A.
Published: June 2012

The antibacterial activity of
N
-formimidoyl thienamycin was compared with those of cefotaxime, cefoperazone, and piperacillin against 536 clinical aerobic isolates.
Synergistic Antibacterial Activity of Clavulanic Acid and Amoxicillin Against β-Lactamase-Producing Strains of
Haemophilus ducreyi
Authors: Girouard Yves C. , Maclean Ian W. , Ronald Allan R. , Albritton William L.
Published: June 2012

The susceptibility of 47 strains of
Haemophilus ducreyi
to amoxicillin, clavulanic acid, and the combination of both drugs was determined by agar dilution susceptibility testing. A synergistic antibacterial activity of the combination was found for β-lactamase-producing strains.
Synergistic activities of fortimicin A and beta-lactam antibiotics against Pseudomonas aeruginosa
Authors: Yamashita K , Kawabe H , Mitsuhashi S
Published: June 2012

The inhibitory and bactericidal activities of fortimicin A (FTM-A) alone against Pseudomonas aeruginosa were compared with those of FTM-A in combination with beta-lactam antibiotics. As tested by the checkerboard method, most beta-lactam antibiotics tested had synergistic effects on the inhibitory activity of FTM-A against one strain of P. aeruginosa. Addition of a sublethal concentration of carbenicillin resulted in a significant increase in the rate of bacterial killing of FTM-A against P. aeruginosa. The antibacterial activity of FTM-A against 50 gentamicin-susceptible and 50 gentamicin-resistant clinical isolates of P. aeruginosa was clearly enhanced by addition of a subinhibitory concentration of carbenicillin or piperacillin.
BRL 17421, a novel beta-lactam antibiotic, highly resistant to beta-lactamases, giving high and prolonged serum levels in humans
Authors: Slocombe B , Basker M J , Bentley P H , Clayton J P , Cole M , Comber K R , Dixon R A , Edmondson R A , Jackson D , Merrikin D J , Sutherland R
Published: June 2012

BRL 17421 is a new semisynthetic beta-lactam antibiotic with an unusual spectrum of antibacterial activity. The compound exhibits exceptional stability to a wide range of bacterial beta-lactamases and is active against the majority of Enterobacteriaceae, including strains highly resistant to many of the penicillins and cephalosporins currently available. Among the clinical isolates of Enterobacteriaceae tested, the frequency of strains resistant to BRL 17421 was found to be low, and there was a slow rate of emergence of resistance during in vitro studies. BRL 17421 was highly active against Haemophilus influenzae and Neisseria gonorrhoeae, including beta-lactamase-producing strains. The compound was markedly less active against Pseudomonas aeruginosa and Bacteroides fragilis than against the Enterobacteriaceae. Against the gram-positive bacteria, BRL 17421 showed a very low level of activity. BRL 17421 was found to be 85% bound to human serum, and the antibacterial activity was diminished two- to fourfold in the presence of human serum. Against experimental infections in mice, the activity of BRL 17421 reflected the properties observed in vitro. Studies in human volunteers showed unusually high and prolonged serum concentrations of the compound after parenteral dosage, with a serum half-life of about 5 h, and approximately 85% of the dose was recovered unchanged in the urine. BRL 17421 was poorly absorbed after oral administration. The compound was well tolerated after intramuscular and intravenous administration in volunteers, with no adverse side effects.
Sensitive bioassay for ketoconazole in serum and cerebrospinal fluid
Authors: Jorgensen J H , Alexander G A , Graybill J R , Drutz D J
Published: June 2012

Ketoconazole is a broad-spectrum antifungal agent which appears promising for treatment of a variety of systemic mycoses. Pharmacokinetic studies are limited due to a lack of readily available methods for quantitation of ketoconazole in serum or cerebrospinal fluid. We developed a rapid, simple bioassay for measurement of ketoconazole alone or in the presence of therapeutic levels of amphotericin B, using an agar diffusion assay incorporating Candida pseudotropicalis. Pairs of 8-mm wells cut in the seeded assay medium were filled with four duplicate ketoconazole standards and duplicate patient specimens. Zones of inhibition were visible after 7 to 8 h of incubation, but were most easily measured after overnight growth. The assay allowed determinations of serum ketoconazole levels as low as 0.3 microgram/ml with a 4.4% coefficient of variation. Thirty-five serum samples from patients receiving the drug were assayed by this method, and the results were compared with the Coccidioides immitis endospore assay. The correlation coefficient between the assays was 0.90. This assay allows any microbiology laboratory to easily and safely determine ketoconazole levels in serum or cerebrospinal fluid.
Pharmacokinetics of new broad-spectrum cephamycin, YM09330, parenterally administered to various experimental animals
Authors: Komiya M , Kikuchi Y , Tachibana A , Yano K
Published: June 2012

The pharmacokinetics of YM09330, a new semisynthetic cephamycin, were determined after intravenous and intramuscular administration to experimental animals. Mean plasma levels of YM09330 at 30 min after intravenous administration of 20 mg/kg were 5.5 micrograms/ml for mice, 17 micrograms/ml for rats, 24 micrograms/ml for rabbits, 42 micrograms/ml for dogs, and 76 micrograms/ml for monkeys; plasma half-lives were 13.0, 15.9, 30.5, 55.5, and 75.6 min, respectively. The half-lives of YM09330 were longer than those of cefmetazole in all species tested. In monkeys, plasma levels of YM09330 were higher and more prolonged than those of cefazolin. In rats and dogs, the concentrations of YM09330 were highest in the kidneys, followed by the liver, plasma, lung, spleen, and heart in that order; they were similar to those of cefazolin in rats. Urinary excretion of YM09330 within 48 h of intravenous administrations was 67% of the dose in mice, 52% in rats, 74% in rabbits, 53% in dogs, and 60% in monkeys. In rats, 48% of the dose of YM09330 was detected in the plasma, urine, or bile. However, small amounts of an antibacterially active tautomer of YM09330 were recovered in the urine of mice, rats, and dogs, whereas large amounts of the tautomer were recovered in the urine of rabbits and monkeys. Serum protein binding of YM09330 was 30% of rats, 51% for rabbits, 39% for dogs, 87% for monkeys, and 91% for humans.
Effect of mixing on rifampin bactericidal activity against staphylococci
Authors: Zinner S H , Husson M , Klastersky J
Published: June 2012

Minimal bactericidal concentrations of rifampin were significantly increased, and serum bactericidal activity from volunteers receiving this drug was significantly decreased by vigorous mixing of microtiter plates before sampling when tested against Staphylococcus aureus and Staphylococcus epidermidis at 10(5) and 10(6) colony-forming units per ml. These results suggest that microtiter estimates of the bactericidal activity of rifampin against staphylococci should be performed after vigorous shaking.
Efficacy of acyclovir against mouse cytomegalovirus in vivo
Authors: Wingard J R , Bender W J , Saral R , Burns W H
Published: June 2012

Acyclovir reduced mortality and organ virus titers in mice inoculated intraperitoneally with 10 50% lethal doses of mouse cytomegalovirus. This susceptibility to acyclovir of a herpesvirus which lacks thymidine kinase is surprising. Alternative phosphorylating enzymes may account for this susceptibility.
Inhibiting Effects of Enflurane and Isoflurane Anesthesia on Measles Virus Replication: Comparison with Halothane
Authors: Knight Paul R. , Nahrwold Michael L. , Bedows Elliott
Published: June 2012

Replication of measles virus in BSC cells was studied in the presence of enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether), a commonly used volatile anesthetic agent, and its isomer, isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether). At clinical concentrations of the anesthetics (up to 4%), cell division was retarded, whereas only minimal toxic cellular effects were observed. The appearance of progeny virus from the cell cultures exposed to these anesthetics was decreased in a dose-related manner. Incorporation of [
3
H]uridine into measles virus nucleocapsids also decreased progressively with increasing anesthetic concentrations. In comparing the inhibition of measles virus replication in the presence of halothane (2-bromo-2-chloro,1,1,1-trifluoroethane), enflurane, or isoflurane, it was found that both inhibition of the appearance of infectious virus at 48 h postinfection and incorporation of [
3
H]uridine into measles virus nucleocapsids were proportional to the anesthetic concentrations. An equivalent degree of effect was produced by anesthetically equivalent concentrations of the three anesthetics (minimal alveolar concentration) but not by absolute concentrations. In addition, recovery of infectious virus synthesis from the inhibition encountered during exposure of infected BSC cells to halothane or isoflurane was also investigated. In cultures exposed to halothane or enflurane, recovery of infectious virus synthesis was rapid and complete. Recovery of virus synthesis was slower after isoflurane removal and did not reach the peak control titers of infected cultures not exposed to the anesthetic. Treatment with halothane resulted in the formation of a preponderance of slowly sedimenting virus nucleocapsid particles which contained less than full-length ribonucleic acids after anesthetic removal. Neither enflurane nor isoflurane treatment of BSC cultures resulted in the formation of significant levels of these slowly sedimenting particles with short genomes after anesthetic removal.
Pharmacology of ceftizoxime compared with that of cefamandole
Authors: Neu H C , Srinivasan S
Published: June 2012

The pharmacokinetics of ceftizoxime, a new beta-lactam antibiotic, were studied in normal, male volunteers and compared with the pharmacokinetics of cefamandole. After administration of 500 mg intramuscularly, ceftizoxime produced a peak level of 13.7 +/- 1 microgram/ml, compared with 13.2 +/- 1.6 microgram/ml for cefamandole. At 4 h, the serum level of ceftizoxime was 4.8 micrograms/ml, and that of cefamandole was 1.9 microgram/ml. At 8 h, ceftizoxime was still detected at 0.73 microgram/ml, whereas cefamandole was not. The half-life of ceftizoxime after intramuscular administration was 1.7 h, compared with 1 h for cefamandole. Serum levels of ceftizoxime and cefamandole after 1 g infused over 30 min were 84 and 88 micrograms/ml, respectively. At 5 h cefamandole was not detectable, whereas ceftizoxime had a serum level of 4.5 micrograms/ml and, at 7 h, 2.1 micrograms/ml. The half-life of ceftizoxime was 1.9 h, compared with 0.78 h for cefamandole. Urinary recovery of ceftizoxime after intramuscular and intravenous administration was 70 and 80%, respectively, compared with 78 and 73% for cefamandole.
Differential activity of potential antiviral nucleoside analogs on herpes simplex virus-induced and human cellular thymidine kinases
Authors: Cheng Y C , Dutschman G , Fox J J , Watanabe K A , Machida H
Published: June 2012

Potential antiviral nucleoside analogs 1-beta-D-arabinofuranosylthymine, the 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-nucleosides of -5-methyluracil, -5-iodouracil, -5-methylcytosine, -5-iodocytosine, and -E-5-(2-bromovinyl)uracil, E-5-(2-bromovinyl)-2'-deoxyuridine, E-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil, and 9-(2-hydroxyethyoxymethyl)guanine were studied to compare their phosphorylation rates relative to thymidine by purified thymidine kinases from human and herpes simplex virus sources. Most of these analogs are capable of being phosphorylated by both human and viral enzymes. On the assumption that inhibition constants (Ki) reflect binding affinity, Ki values were determined for these analogs with the same thymidine kinases. In general, these analogs have a greater affinity for the viral enzymes. The amount of the analogs phosphorylated to the monophosphate form, which is presumably necessary to produce cytotoxic effects, was determined by the combined effects of phosphorylation rates and binding affinities. All of these analogs act as preferential substrates for the viral thymidine kinases at low concentrations, which may be one of the main reasons for their selective antiviral action.
In vitro activity of MK0787 (N-formimidoyl thienamycin) and other beta-lactam compounds against Bacteroides spp
Authors: Nasu M , Maskell J P , Williams R J , Williams J D
Published: June 2012

The susceptibilities of 82 strains of the Bacteroides fragilis group to eight beta-lactam compounds, lincomycin, and metronidazole were determined by using an agar dilution technique. MK0787 (N-formimidoyl thienamycin) was the most active compound, inhibiting all strains at a concentration of 1 microgram/ml. Metronidazole was the only other drug of similar activity. Of the beta-lactam compounds, cefoxitin and MK0787 showed uniform activity against all species, whereas most other compounds were relatively less active against Bacteroides distasonis and Bacteroides thetaiotaomicron than against B. fragilis and Bacteroides vulgatus. Using a well diffusion technique, we determined the relative stability of each beta-lactam compound to sonicated cultures of selected resistant strains. Whereas MK0787 was completely stable to inactivation--and with one exception, cefoxitin was also--ceftriaxone, cefotaxime, cephaloridine, and cefoperazone always showed some inactivation, often quite substantial. Moxalactam and ceftazidime were completely stable to some of the enzyme preparations.
Inhibition of ribonucleic acid polymerase by a bacteriocin from Bacteroides fragilis
Authors: Mossie K G , Robb F T , Jones D T , Woods D R
Published: June 2012

The Bacteroides fragilis bacteriocin which inhibits ribonucleic acid (RNA) polymerase activity had a narrow activity spectrum in vivo and only inhibited the growth of certain B. fragilis strains. In vitro the bacteriocin was not specific and inhibited RNA polymerases from widely diverse bacterial genera. RNA polymerases from rifampin-resistant strains of Bacteroides thetaiotaomicron and Clostridium acetobutylicum were resistant to the bacteriocin in vitro. Purified bacteriocin bound to partially purified RNA polymerase, and both proteins were cosedimented in a glycerol gradient. In the RNA polymerase reaction, the bacteriocin acted as a competitive inhibitor for adenosine, cytidine, and uridine 5'-triphosphates and as a noncompetitive inhibitor for guanosine 5'-triphosphate. The bacteriocin did not inhibit RNA polymerase from chicken embryos.
Mode of action of pamamycin in Staphylococcus aureus
Authors: Chou W G , Pogell B M
Published: June 2012

Pamamycin was previously identified as a stimulator of aerial mycelium formation in Streptomyces alboniger and as a new antibiotic. Studies in Staphylococcus aureus grown in brain heart infusion broth showed that this antibiotic was bacteriostatic at 0.1 to 0.3 U/ml and bactericidal at 0.5 U/ml or higher. At concentrations which inhibited growth ca. 40%, pamamycin inhibited the uptake of nucleosides and Pi, as well as purine and pyrimidine bases, and the incorporation of these precursors into nucleic acids. Under the same conditions, the antibiotic had no effect on protein and cell wall synthesis, glucose utilization, or the uptake of amino acids, 2-deoxyglucose, or Mn2+. Further studies suggested that the primary action of pamamycin was on transport processes rather than de novo ribonucleic acid and deoxyribonucleic acid synthesis. Direct in vitro studies of nucleoside transport with isolated membrane vesicles confirmed this conclusion. Pamamycin bound tightly to bacterial membranes and induced significant release of ultraviolet-absorbing material at bactericidal concentrations. It was concluded that the mechanism of growth inhibition involves alteration of membrane-associated cellular functions. Inhibition of Pi transport is a likely primary target for this effect.
Antibacterial properties of alafosfalin combined with cephalexin
Authors: Atherton F R , Hall M J , Hassall C H , Holmes S W , Lambert R W , Lloyd W J , Nisbet L J , Ringrose P S , Westmacott D
Published: June 2012

The phosphonopeptide alafosfalin (L-alanyl-L-1-aminoethylphosphonic acid) exhibited synergy in vitro and in animal studies against a range of bacterial genera when combined with cephalexin. Alafosfalin also showed synergy with mecillinam and, to a much lesser extent, with ampicillin. Synergy with cephalexin was more pronounced when the bacteria were relatively insensitive to the beta-lactam component. The action of this combination involved both an inhibitory and a bacteriolytic mechanism which was abolished by concurrent treatment with the aminopeptidase inhibitor, bestatin. Regrowth of subpopulation resistant to either component was markedly reduced by the combination. The potential of alafosfalin combined with cephalexin for use in therapy is discussed.
Arginine regulation of gramicidin S biosynthesis
Authors: Poirier A , Demain A L
Published: June 2012

Several amino acids are known to affect the gramicidin S producer Bacillus brevis ATCC 9999 with respect ot growth, soluble gramicidin S synthetase formation, antibiotic production, or a combination of these. Our studies confirmed that arginine has paradoxical effects on the B. brevis fermentation; it markedly increased growth and antibiotic production, yet decreased the soluble heavy gramicidin S synthetase activity. We found that arginine did not repress heavy gramicidin S synthetase. The amino acid stimulated growth and increased specific antibiotic production presumably by supplying a limiting precursor (ornithine) for gramicidin S synthesis. Although the amino acid decreased the specific activity of the soluble heavy gramicidin S synthetase, it markedly increased the particulate enzyme activity which persisted hours after the soluble heavy gramicidin S synthetase disappeared. One percent arginine was the optimum level for growth and gramicidin S production. After growth in 1% arginine, heavy synthetase activity in the particulate fraction more than doubled. We propose that arginine leads to the soluble enzyme becoming membrane bound and more stable in vivo. Although we found arginine capable of inhibiting the action of soluble heavy gramicidin S synthetase, this was not the mechanism involved in the lowering of soluble heavy gramicidin S synthetase specific activity.
Concentrations of kanamycin and amikacin in human gallbladder bile and wall
Authors: Hansbrough J F , Clark J E , Reimer L G
Published: June 2012

The concentrations of amikacin and kanamycin were determined in the serum, gallbladder bile, and gallbladder wall of 20 patients undergoing elective cholecystectomy. Of 20 patients, 14 received 500 mg of amikacin intramuscularly and 6 received 500 mg of kanamycin intramuscularly at various times before surgery. In patients receiving kanamycin, detectable levels appeared in bile within 90 min after drug administration, and in five of six patients concentrations ranged from 1.9 to 23 micrograms/ml. Levels of kanamycin in gallbladder wall ranged from 8.0 to 14 micrograms/g. In patients receiving amikacin, detectable levels appeared in bile within 48 min after drug administration and ranged from 1.3 to 7.5 micrograms/ml in 12 of 14 patients. Levels of amikacin in gallbladder wall ranged from 4.7 to 34 micrograms/g. The presence of an obstructed cystic duct did not preclude the entry of either antibiotic into gallbladder bile, and this may reflect passage of antibiotic through the gallbladder wall rather than accumulation via bile secretion.