bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of concentrations of rifampin and a new rifamycin derivative, DL 473, in canine bone
Authors: Iversen P , Nielsen O S , Jensen K M , Madsen P O
Published: June 2012

Constant-infusion experiments were performed in 14 dogs to determine the penetration into bone of rifampin and a new C-3 substituted rifamycin, DL 473. The drugs were assayed in cortical bone and medulla from tibia-femur and cortical and cancellous bone from rib. After identical dosage, the concentrations of DL 473 appeared to be higher, except in the medulla, although the serum concentrations of rifampin were almost twice as high as those for DL 473. The concentrations of both drugs in all bone areas were several times higher than their minimum inhibitory concentrations against pathogenic Staphylococcus aureus.
Ceftriaxone pharmacokinetics in newborn infants
Authors: McCracken G H , Siegel J D , Threlkeld N , Thomas M
Published: June 2012

Ceftriaxone pharmacokinetics were determined in 40 newborn infants who were 1 to 45 days of age. Mean peak plasma concentrations of 136 to 173 micrograms/ml were observed at the completion of a 15-min intravenous infusion of 50 mg of ceftriaxone per kg. Mean half-life values were 5.2 to 8.4 h, and mean plasma clearances were 0.7 to 1.8 ml/min. Rectal swab cultures from 14 of 16 infants had either reduced numbers of aerobic and anaerobic bacteria or no growth during therapy. A once-daily dosage schedule is suggested for ceftriaxone therapy in newborn infants.
Cefoperazone pharmacokinetics in normal subjects and patients with cirrhosis
Authors: Boscia J A , Korzeniowski O M , Snepar R , Kobasa W D , Levison M E , Kaye D
Published: June 2012

The pharmacokinetics of cefoperazone were studied and compared in six normal subjects and six patients with severe liver disease. All subjects received a 2-g intravenous infusion of cefoperazone over 15 min. Significantly different results were noted between normal subjects and patients with cirrhosis (range [mean]) for the following: peak serum concentrations (203 to 345 [239] versus 82 to 206 [141] micrograms/ml; P less than 0.01); serum beta half-lives (1.0 to 1.8 [1.5] versus 2.3 to 9.9 [4.5] h; P less than 0.05); renal excretion (17 to 27 [21] versus 32 to 60 [50]%; P less than 0.01); and apparent volumes of distribution at steady state (4.1 to 7.8 [6.3] versus 12.7 to 23.8 [15.9] liters/1.73 m2; P less than 0.01). Lower peak serum levels in the patients with cirrhosis were probably related to an increased apparent volume of distribution secondary to ascites and to decreased serum protein binding of cefoperazone. Longer beta half-lives in the patients with cirrhosis were probably secondary to both decreased hepatic excretion caused by severe liver disease and to increased apparent volume of distribution. However, the longest beta half-life among the patients with cirrhosis was in a subject with a serum creatinine level of 2.1 mg/dl. We conclude that, although mild to moderate impairment of cefoperazone excretion occurs in patients with hepatic disease, adjustment of dosage may be necessary only with concomitant renal insufficiency.
In vitro activity of teichomycin and vancomycin alone and in combination with rifampin
Authors: Varaldo P E , Debbia E , Schito G C
Published: June 2012

The antibacterial activity of teichomycin, a glycopeptide antibiotic similar to vancomycin, has been evaluated in vitro and compared with that of vancomycin. Test strains included 130 staphylococci and 132 streptococci, with representatives of the major currently recognized species or groups, and lesser numbers of clostridia, propionibacteria, and group JK bacteria. Teichomycin was found to be more active than vancomycin. Its minimum inhibitory concentration (MIC) was two- to fourfold lower than that of vancomycin with staphylococci and anaerobic bacteria, and two- to eightfold lower with streptococci. No significant differences were observed with group JK bacteria. For most strains tested, minimum bactericidal concentrations (MBCs) of both teichomycin and vancomycin either equalled or exceeded by twofold the respective MICs. Higher MBC-to-MIC ratios were obtained for enterococci and pneumococci with both antibiotics. Both teichomycin and vancomycin showed similar in vitro interactions with rifampin in combination tests. Neither antagonism nor (with very few exceptions) synergism occurred.
Serum bactericidal activity of ceftazidime and cefoperazone alone or in combination with amikacin against Pseudomonas aeruginosa and Klebsiella pneumoniae
Authors: Van Laethem Y , Lagast H , Klastersky J
Published: June 2012

Sera of volunteers receiving ceftazidime (2 g) or amikacin (500 mg), alone or in combination, or cefoperazone (2, 4, or 6 g) or cefoperazone (2 g) with amikacin (500 mg) were evaluated for bactericidal activity against Klebsiella pneumoniae and Pseudomonas aeruginosa. Serum bactericidal activities were similar for ceftazidime and ceftazidime plus amikacin, but were definitely lower for amikacin alone. Against P. aeruginosa, a 6-g dose of cefoperazone resulted in a higher frequency of peak serum bactericidal activities greater than or equal to 1:8 than a 2-g dose of cefoperazone plus amikacin. Killing studies, performed in 1:8 diluted serum, demonstrated a higher killing rate for cefoperazone plus amikacin than for a 6-g dose of cefoperazone, the more resistant P. aeruginosa excepted. Emergence of resistance was found with a 2-g dose of cefoperazone for K. pneumoniae and with a 6-g dose of cefoperazone for P. aeruginosa, but not with cefoperazone plus amikacin.
Inhibition of lysosomal phospholipases by aminoglycoside antibiotics: in vitro comparative studies
Authors: Carlier M B , Laurent G , Claes P J , Vanderhaeghe H J , Tulkens P M
Published: June 2012

Aminoglycoside antibiotics induce an early and characteristic lysosomal phospholipidosis in cultured fibroblasts and in kidney tubular cells. We have recently demonstrated an inhibition of lysosomal phospholipases A1 and A2 by gentamicin and amikacin in vitro. In vivo, gentamicin decreases the activity of phospholipase A1 (Laurent et al., Biochem. Pharmacol. 31:3861-3870, 1982). In the present study, we examined 14 aminoglycosides for in vitro inhibition of phospholipases. To mimic the situation prevailing in lysosomes, the enzymatic activities were assayed with phospholipid vesicles (liposomes) with a composition similar to that of lysosomal phospholipids (phosphatidylcholine, sphingomyelin, phosphatidylinositol, cholesterol; 4:4:3:5.5, molar ratio). We measured the hydrolysis of 1-palmitoyl-2-[1-14C]oleoyl phosphatidylcholine contained in the liposomes by a soluble fraction of highly purified lysosomes isolated from rat liver. Similar IC50S (concentrations causing 50% inhibition of enzymatic activity) were observed for dibekacin, gentamicin (with no major difference between C1, C1a, or C2), netilmicin, tobramycin, and kanamycin B. Sisomicin was slightly more inhibitory. Kanamycin A, N1-(L-4-amino-2-hydroxy-1-oxobutyl)dibekacin, and amikacin showed increasing IC50S. Streptomycin caused the least inhibition. Octa- and tetramethylkanamycin A are much less inhibitory than the parent drug. These results point to the number, the nature, and the respective positions of the cationic groups as essential determinants in causing inhibition of phospholipid breakdown. The binding of three aminoglycosides (gentamicin, amikacin, streptomycin) to the liposomes at pH 5.4 was also measured by gel permeation and was found to be related to the respective inhibitory potency of each drug. Insofar as lysosomal phospholipidosis is an early sign of intoxication by aminoglycosides, these results may serve as a basis for the development or screening of less toxic compounds in this class of antimicrobial agents.
In vitro susceptibility patterns of methicillin-resistant and-susceptible Staphylococcus auerues strains in a population of parenteral drug abusers from 1972 to 1981
Authors: Markowitz N , Pohlod D J , Saravolatz L D , Quinn E L
Published: June 2012

Since 1980, infections caused by methicillin-resistant (MR) Staphylococcus aureus have been epidemic among Detroit-area parenteral drug abusers. Because of the increasing importance of this pathogen, in vitro susceptibilities were compared for 39 isolates of MR S. aureus from 1980 to 1981, and for 56 strains of methicillin-susceptible (MS) S. aureus from 1972 to 1981, recovered from drug abusers with community-acquired infections. Agar dilution studies were performed at 35 degrees C, and minimal inhibitory concentrations were determined after incubation for 18 and 48 h. MR S. aureus exhibited cross-resistance to other beta-lactam antibiotics which frequently required 48 h for expression. MR S. aureus isolates were also resistant to tetracycline, clindamycin, tobramycin, and amikacin. All MR S. aureus isolates investigated synthesized an aminoglycoside 4'-nucleotidyltransferase. Emergence of resistance to cefotaxime, tetracycline, and clindamycin was noted among current MS S. aureus isolates. Vancomycin, fusidic acid, trimethoprim/sulfamethoxazole, and rifampin were the most active agents against MR S. aureus and were equally effective against MS S. aureus.
Comparative in vitro activity of Sch 29,482, a new oral penem, against Neisseria gonorrhoeae
Authors: Khan M Y , Gruninger R P , Nelson S M , Simpson M L
Published: June 2012

The in vitro activity of Sch 29,482, a new oral beta-lactam antimicrobial agent, was compared with those of norfloxacin, rosoxacin, ampicillin, erythromycin, and tetracycline against 142 Neisseria gonorrhoeae strains. Sch 29,482 was as active as norfloxacin and rosoxacin. Its activity was greater than the other three antimicrobial agents. It inhibited 90% of the isolates, regardless of beta-lactamase activity, at a concentration of less than or equal to 0.06 micrograms/ml.
In vitro activity of rifampin in combination with oxacillin against Staphylococcus aureus
Authors: Maduri Traczewski M , Goldmann D A , Murphy P
Published: June 2012

The in vitro activity of rifampin alone and in combination with oxacillin was determined for 75 Staphylococcus aureus strains (64 susceptible and 11 resistant to oxacillin). Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were determined by broth microdilution; antibiotic combinations were evaluated by microdilution checkerboard and time-kill studies. The 90% MIC of rifampin was less than or equal to 0.015 micrograms/ml after both 24 and 48 h of incubation. The 90% MBC of rifampin was less than or equal to 2.0 micrograms/ml on subculture at 24 h of incubation and less than or equal to 0.5 micrograms/ml on subculture at 48 h. MIC checkerboards with oxacillin-susceptible strains revealed an additive or indifferent effect in 35 strains (55%) and antagonism in 29 strains (45%). MBC checkerboards performed by subculture at 24 h demonstrated antagonism for all but one of the oxacillin-susceptible strains, with sub-MBCs of rifampin impairing the bactericidal activity of oxacillin. MBC checkerboards performed by 48-h subculture revealed antagonism with 37 strains (58%); in 26 additional strains (40%), a synergistic, additive, or indifferent effect was observed at low antibiotic concentrations, but antagonism was seen at higher concentrations. Time-kill studies tended to show indifference rather than antagonism with oxacillin plus rifampin. In checkerboards performed with oxacillin-resistant strains, the addition of rifampin did not improve oxacillin inhibitory or bactericidal activity to a clinically significant extent; however, the addition of oxacillin improved the bactericidal activity of rifampin at easily achievable serum concentrations.
Effects of cloned interferon alpha 2 in normal volunteers: febrile reactions and changes in circulating corticosteroids and trace metals
Authors: Scott G M , Ward R J , Wright D J , Robinson J A , Onwubalili J K , Gauci C L
Published: June 2012

Six healthy volunteers were given single intramuscular injections of an ascending dose schedule of human interferon alpha 2 (Hu IFN alpha 2) from Escherichia coli. At a dose of 3 X 10(6) U, all of the volunteers had febrile reactions with influenza-like symptoms as previously described for purified natural leukocyte interferon. Significant rises in serum 11-hydroxycorticosteroids and falls in plasma zinc levels were observed at this highest dose. Although there was a reduction in the febrile reaction complex, the simultaneous administration of indomethacin with a "toxic" dose of interferon did not alter the changes in white cells, corticosteroids, or trace metals. Nonspecific effects must be considered in the therapeutic activity of interferon.
Isolation of trimethoprim-resistant, sulfonamide-susceptible Enterobacteriaceae from urinary tract infections
Authors: Towner K J , Smith M A , Cowlishaw W A
Published: June 2012

The isolation of trimethoprim-resistant, sulfonamide-susceptible Enterobacteriaceae causing urinary tract infections is reported. The appearance of these strains followed the introduction of trimethoprim alone for use as treatment. Trimethoprim resistance was attributable to plasmids or transposons less frequently in sulfonamide-susceptible Escherichia coli isolates than in sulfonamide-resistant strains.
Bacteriological studies of the enteric flora of patients treated with bicozamycin (CGP 3543/E) for acute nonparasitic diarrhea
Authors: Harford P S , Murray B E , DuPont H L , Ericsson C D
Published: June 2012

During a therapeutic trial of bicozamycin (BI) for traveler's diarrhea, aerobically grown, gram-negative bacteria, predominantly Escherichia coli, were decreased by 2 to 3 logs per g of stool; the number of BI-resistant gram-negative bacteria did not increase. Resistant species were most often Citrobacter freundii, Klebsiella pneumoniae, and Morganella morganii, and few BI-resistant E. coli strains were isolated. Cross-resistance between BI and other antimicrobial agents was not found. Resistance to BI could not be transferred or mobilized to an E. coli K-12 recipient.
Anti-herpesvirus activity of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine
Authors: Smee D F , Martin J C , Verheyden J P , Matthews T R
Published: June 2012

The antiherpetic effects of a novel purine acyclic nucleoside, 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), were compared with those of acyclovir in cell cultures and in mice. The modes of action of DHPG and acyclovir were similar in that herpes thymidine kinase phosphorylated each compound, and both agents selectively inhibited viral over host cell DNA synthesis. In 50% plaque reduction assays in Vero cells, the drugs inhibited herpes simplex virus types 1 and 2 thymidine kinase-positive strains at 0.2 to 2.4 microM. DHPG was markedly more active than acyclovir against human cytomegalovirus (50% inhibitory doses were 7 and 95 microM, respectively). Each nucleoside inhibited uninfected cell macromolecule synthesis and cell proliferation at concentrations far above those required to inhibit herpes simplex virus replication. Although the two compounds had many similarities in their behavior in vitro, the important difference was the superior performance of DHPG against herpesvirus-induced encephalitis and vaginitis in vivo. Thus, mortality in mice infected with herpesvirus type 2 was reduced 50% by daily doses of 7 to 10 mg of DHPG/kg, whereas an equally effective daily dose of acyclovir was approximately 500 mg/kg. DHPG at a daily dose of 50 mg/kg was also superior to acyclovir at 100 mg/kg per day in its inhibition of herpetic vaginal lesions in mice.
Automated fluorescence polarization immunoassay for monitoring streptomycin
Authors: Schwenzer K S , Anhalt J P
Published: June 2012

The fluorescence polarization immunoassay technique has been used previously for the assay of vancomycin and the aminoglycoside antibiotics (gentamicin, tobramycin, and amikacin). We extended this technique to assay streptomycin. Fluorescein-labeled streptomycin was used as the tracer, and antiserum specific for streptomycin was raised in rabbits by conventional procedures. Tracer, sample, and diluted antiserum were combined, and the polarization of tracer fluorescence was determined in a specially designed fluorometer (Abbott TDx). Because of the instrument design, the possibility of fluorescent interferences was eliminated. The coefficient of variation within run was 4% (n = 5), and between run it was 5% (n = 5). We compared the fluorescence polarization immunoassay technique (TDx streptomycin) with a conventional bioassay, using Bacillus subtilis for clinical specimens (n = 39). A least-squares linear regression analysis gave a slope of 1.16, an intercept of 2.41 mg/liter, and a correlation coefficient of 0.885. Repeat analyses by both techniques showed that the largest discrepancies could be explained by the imprecision of the bioassay.
Lack of influence of commonly used drugs on bioassay indicator organisms
Authors: DiPiro J T , Taylor A T , Steele J C
Published: June 2012

Many commonly used pharmaceutical agents have been found to inhibit bacterial growth in vitro. Determinations of antimicrobial concentrations in sera of patients taking nonrecognized antibacterial agents could possibly be altered if bioassay systems are utilized for the determinations. We therefore attempted to determine the in vitro effect of commonly used drugs on bioassay indicator organisms. Fifty-one different agents (antihistamines, anticholinergics, central nervous system agents, cardiovascular agents, analgesics, steroids, muscle blockers, and other miscellaneous agents) were tested for inhibition or enhancement of the growth of Bacillus subtilis, Staphylococcus aureus, Micrococcus luteus, and Klebsiella pneumoniae. None of the agents tested exhibited any effect on standard in vitro bioassay organisms. Nortriptyline hydrochloride inhibited the growth of B. subtilis and M. luteus at a concentration of 500 micrograms/ml (zones of inhibition, 14 and 13 mm, respectively), but no inhibition was observed with concentrations of 50 micrograms/ml or lower.
Activity of AT-2266 compared with those of norfloxacin, pipemidic acid, nalidixic acid, and gentamicin against various experimental infections in mice
Authors: Nakamura S , Nakata K , Katae H , Minami A , Kashimoto S , Yamagishi J , Takase Y , Shimizu M
Published: June 2012

AT-2266 (1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1, 8-naphthyridine-3-carboxylic acid) showed marked activity in vivo when administered orally to mice bearing systemic, pulmonary, dermal, or urinary tract infections due to variety of organisms. The activity of AT-2266 was uniformly higher than those of norfloxacin, pipemidic acid, and nalidixic acid against all of the infections. The activity of AT-2266 administered orally was almost comparable to that of gentamicin administered subcutaneously against urinary tract infections due to gram-negative organisms but was generally lower against other infections. AT-2266 exhibited significant activity against infections due to gentamicin-resistant and nalidixic acid-resistant organisms.
In vitro study of bacterial growth inhibition in concentrated sugar solutions: microbiological basis for the use of sugar in treating infected wounds
Authors: Chirife J , Herszage L , Joseph A , Kohn E S
Published: June 2012

The use of sugar for the treatment of infected wounds was investigated in in vitro experiments with bacteria pathogenic to humans, such as Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus. Studies showed that solutions of appropriate sugar concentration incubated at pH 7.0 and 35 degrees C were lethal to the bacterial species studied. On the basis of these results, it is proposed that an important function of sugar in the treatment of infected wounds is to create an environment of low water activity (aw), which inhibits or stresses bacterial growth.
Comparison of Susceptibilities of Anaerobic Bacteria to Cefmenoxime, Ceftriaxone, and Other Antimicrobial Compounds
Authors: Pollock Helen M. , Holt Jean , Murray Cecilia
Published: June 2012

The minimal inhibitory concentrations of cefmenoxime, cefotaxime, cefoxitin, ceftriaxone, chloramphenicol, clindamycin, and moxalactam were determined by agar dilution for 202 clinical isolates of anaerobic bacteria. Cefoxitin and moxalactam were the most active among the cephalosporin-like compounds.
Pharmacology of ketoconazole suspension in infants and children
Authors: Ginsburg C M , McCracken G H , Olsen K
Published: June 2012

The pharmacokinetics of ketoconazole administered as either a commercially prepared suspension or as a crushed tablet in applesauce were studied in 12 children. The mean peak plasma concentration of ketoconazole and the area under the plasma time-concentration curve were approximately twofold greater with the suspension than with the crushed tablets.
Antimicrobial Susceptibilities of Coagulase-Negative Staphylococci Isolated from Urinary Infections
Authors: Bourgault Anne-Marie , Gauvreau Léo
Published: June 2012

The susceptibilities of 107 urinary isolates of coagulase-negative staphylococci to 19 antibiotics was determined by an agar dilution technique. Major differences in the antimicrobial susceptibilities of species of coagulase-negative staphylococci were observed.
Staphylococcus epidermidis
was more resistant to a wider spectrum of antibiotics than was
Staphylococcus saprophyticus
.
Effect of probenecid on the pharmacokinetics of cefmenoxime
Authors: Sennello L T , Quinn D , Rollins D E , Tolman K G , Sonders R C
Published: June 2012

In this study, we were concerned with the effect of probenecid on the pharmacokinetics of 1,000 mg of cefmenoxime administered over a 30-min period by intravenous infusion. Each of a total of 10 subjects received cefmenoxime twice, once with and once without adjunctive probenecid. The data were fit by iterative nonlinear regression procedures to a two-compartment open pharmacokinetic model, with elimination from the central compartment. The mean calculated peak concentration, area under the curve from zero to infinity, and half-life without probenecid were 78.1 micrograms/ml, 77.2 micrograms . h/ml, and 1.14 h, respectively. When cefmenoxime was administered with probenecid, these values were 86.7 micrograms/ml, 158.2 micrograms . h/ml, and 1.78 h, respectively. Averages of about 55 and 46% of the administered doses were recovered in urine samples collected at 0 through 24 h for doses administered without and with probenecid, respectively. The mean corrected renal drug clearance was 159 and 66 ml/min without and with probenecid, respectively. Statistical significance (P less than 0.05) was demonstrated for the differences in beta half-life, (K/net), calculated peak concentration, area under the curve from 0 to infinity, and renal clearance, but not for K21, K12, volume of distribution, or alpha-phase distribution rate constant. The results of this study indicate that tubular secretion is the predominant mechanism of clearance for cefmenoxime and that probenecid alters the pharmacokinetics of the compound by competitively inhibiting its tubular secretion without affecting either the rate or the extent of its distribution.
Pharmacokinetics of amdinocillin in healthy adults
Authors: Meyers B R , Jacobson J , Masci J , Srulevitch E , Hirschman S Z
Published: June 2012

The pharmacokinetics of amdinocillin (mecillinam) were determined in 10 healthy volunteers. Single doses of 10 and 15 mg/kg of body weight were administered intravenously and intramuscularly in a crossover study. Plasma concentrations of amdinocillin were determined by microbiological assay. Mean peak plasma concentrations were 49 and 87 micrograms/ml after intravenous doses of 10 and 15 mg/kg, respectively. The terminal half-life value of 0.89 h was similar for both doses. After intramuscular injections, the mean concentration of drug in plasma was 26.2 micrograms/ml for the 10-mg/kg dose and 29.6 micrograms/ml for the 15-mg/kg dose, with terminal half-lives of 0.96 and 0.86 h, respectively. The mean apparent volumes of distribution at steady state were 18 and 16 liters/100 kg for the intravenous doses of 10 and 15 mg/kg, respectively. Drug concentrations in plasma at 4 h were above the minimal inhibitory concentrations for gram-negative organisms categorized as susceptible to this drug.
Roles of ribosomal binding, membrane potential, and electron transport in bacterial uptake of streptomycin and gentamicin
Authors: Bryan L E , Kwan S
Published: June 2012

The effects of a set of conditions on aminoglycoside uptake were determined. Membrane vesicles either with a membrane potential (delta psi) of -125 mV (adequate to drive lysine uptake) or with succinate, lactate, or phenazine methosulfate did not accumulate gentamicin unless components of protein synthesis were included. Ribosomally resistant (rpsL) Escherichia coli cells demonstrated energy-dependent phase II uptake similar to that of a streptomycin-susceptible strain of E. coli when treated with 100 micrograms of puromycin per ml. Puromycin (100 micrograms/ml) also increased the uptake of the cationic compounds polyamine and arginine. These studies support a role of protein synthesis in aminoglycoside uptake and in the development of energy-dependent phase II. delta psi of cells did not increase either at the initiation of or during energy-dependent phase II, showing that energy-dependent phase II is not due to an elevation of delta psi. In a Bacillus subtilis system, significant streptomycin uptake requires a threshold value of delta psi which varies depending upon the concentration of streptomycin used. At 25 micrograms/ml, the uptake of streptomycin reached maximal levels after exceeding the threshold value, whereas at 100 micrograms/ml there was a gradual increase of the uptake to the maximal after the threshold value was exceeded. Several studies supported the view that electron transport has a specific role other than its requirement to produce the cellular delta psi. The uptake of gentamicin was stimulated to a greater extent by phenazine methosulfate-ascorbate than by the ionophore nigericin in strains of E. coli, although nigericin stimulated delta psi to a greater degree. Cells with 25% of the normal quinone concentration had delta psi values identical to cells with the normal quinone concentration, but the quinone-deficient cells had a significantly lower rate of gentamicin uptake. KCN prevented gentamicin uptake but did not prevent the development of delta psi. The effects of ubiquinone depletion in an E. coli strain were more evident on gentamicin uptake than on ATP-driven glutamine transport or proton motive force-driven proline transport, consistent with a specific requirement for quinones in aminoglycoside uptake. A detailed explanation of the mechanism of accumulation of streptomycin and gentamicin and a proposed mechanism for killing bacterial cells by these agents have been provided.
Ceftriaxone distribution between maternal blood and fetal blood and tissues at parturition and between blood and milk postpartum
Authors: Kafetzis D A , Brater D C , Fanourgakis J E , Voyatzis J , Georgakopoulos P
Published: June 2012

The penetration of ceftriaxone into the fetus at parturition was studied in 17 subjects. Despite its high protein binding, ceftriaxone quickly reached the umbilical cord blood, amniotic fluid, and placenta, achieving substantial concentrations, which then disappeared, with elimination half-lives of approximately 6 h, identical to that of the mother. The elimination half-life of ceftriaxone of 5 to 6 h in these mothers was somewhat shorter than that reported for normal subjects. The concentrations of ceftriaxone achieved in fetal tissues were sufficient for therapeutic effects. The penetration of ceftriaxone into milk was studied 3 days postpartum in 20 other patients. This antimicrobial agent entered breast milk rapidly and disappeared with a half-life of 12 to 17 h. The concentrations achieved were only 3 to 4% of those in maternal serum and were most likely of little clinical relevance.
Pharmacokinetics of piperacillin in subjects with various degrees of renal function
Authors: Welling P G , Craig W A , Bundtzen R W , Kwok F W , Gerber A U , Madsen P O
Published: June 2012

The pharmacokinetics of piperacillin were examined after single intravenous doses to three groups of male patients with creatinine clearances of greater than or equal to 60 (group I), greater than or equal to 20 but less than 60 (group II), and less than 20 (group III) ml/min per 1.73 m2. Each of 32 patients received either 1 or 4 g of piperacillin as a bolus injection. Three patients received both doses. After a rapid 0.5- to 1-h distribution phase, antibiotic levels in serum declined monoexponentially. After the 1-g dose, mean peak piperacillin levels in serum were 60, 103, and 67 micrograms/ml and the beta phase elimination half-lives were 1.0, 1.6, and 3.9 h in groups I, II, and III, respectively. After the 4-g dose, the respective mean peak piperacillin levels in serum were 329, 232, and 262 micrograms/ml and beta phase half-lives were 1.4, 2.3, and 2.6 h in the three groups. There was no clear evidence of significant dose-dependent effects on any pharmacokinetic parameters in any of the groups. Piperacillin levels in urine were far higher than those in serum, generally exceeding the minimal inhibitory concentrations for susceptible organisms during the 24 h after both the 1- and the 4-g dose. Piperacillin dosage modification is required only in patients with severe renal impairment.
Comparison of the nephrotoxicity and auditory toxicity of tobramycin and amikacin
Authors: Gatell J M , San Miguel J G , Zamora L , Araujo V , Bonet M , Bohé M , Jimenez de Anta M T , Farré M , Elena M , Ballesta A , Marin J L
Published: June 2012

A total of 157 patients were treated with tobramycin or amikacin in a controlled prospective randomized trial. Dosages were adjusted to renal function according to a nomogram. Trough and peak aminoglycoside levels were available at the end of the trial. Of the above total, 113 recipients of nine or more doses of tobramycin or six or more doses of amikacin, without other apparent cause of renal failure, were evaluated for nephrotoxicity. Thirty-six patients were evaluated for auditory toxicity. The patients in groups evaluated for either nephrotoxicity or auditory toxicity were similar with respect to intensity and etiology of bacterial disease, concurrent exposure to other antimicrobial drugs, age and sex distribution, initial serum creatinine level, and total dose and duration of antimicrobial therapy. Nephrotoxicity of similar severity developed in 4 of 59 (6.8%) recipients of tobramycin and in 7 of 54 (13.1%) recipients of amikacin (P greater than 0.05). Mild auditory toxicity developed in 3 of 19 (15.7%) recipients of tobramycin and in 2 of 17 (11.7%) recipients of amikacin (P greater than 0.05). When patients with abnormally high mean trough or peak aminoglycoside levels were excluded from comparison, nephrotoxicity was 6.12 and 5.12% (P greater than 0.05) and auditory toxicity was 17.6 and 7.69% (P greater than 0.05) in the groups given tobramycin and amikacin, respectively. We conclude that the nephrotoxicity and auditory toxicity of amikacin and tobramycin are not significantly different and that such toxicities are indeed infrequent events when the dosages of these drugs are adjusted to hold blood levels within the safe boundaries suggested by the studies of others.
Susceptibility of phosphonoformic acid-resistant herpes simplex virus variants to arabinosylnucleosides and aphidicolin
Authors: Bastow K F , Derse D D , Cheng Y C
Published: June 2012

A plaque-reduction assay was used to examine the susceptibility of five phosphonoformic acid-resistant variants of herpes simplex virus type 1 to arabinosylnucleosides and aphidicolin. These viruses were cross-resistant to arabinosylhypoxanthine and to arabinosyladenine when tested in the absence of deoxycoformycin, a deaminase inhibitor. In the presence of deoxycoformycin, no cross-resistance between arabinosyladenine and phosphonoformic acid was observed. The two variants tested were cross-resistant to arabinosylthymine, and all five variants were collaterally susceptible to aphidicolin inhibition.
Mechanism of resistance to some cephalosporins in Staphylococcus aureus
Authors: Kono M , Sasatsu M , O'Hara K , Shiomi Y , Hayasaka T
Published: June 2012

The mechanism of resistance to some cephalosporins in Staphylococcus aureus strains was investigated with high-pressure liquid chromatography and nuclear magnetic resonance spectrometry. Drug inactivation by penicillinase was found to be the main mechanism of resistance to cefazolin, cephaloridine, and cephalothin in S. aureus.
Clinical trial of cefonicid for treatment of skin infections
Authors: Gremillion D H , Winn R E , Vandenbout E
Published: June 2012

Twenty patients with skin and soft-tissue infections were treated with parenteral cefonicid. Cultures obtained in cellulitis cases from an aspirate of a leading edge of inflammation were positive in 42% of these patients. Pathogens isolated were Staphylococcus aureus (six strains), Proteus mirabilis (one strain), and Streptococcus agalactiae. Adverse effects were pain on intramuscular injection (two patients), rash (one patient), and positive Coombs test (one patient). All side effects were mild and none required discontinuing antibiotic therapy. A single treatment failure occurred in a patient with an undrained perirectal abscess. Cefonicid may be a useful drug in the treatment of skin and soft-tissue infections. The long half-life of cefonicid (4.8 h) is a valuable advantage and may facilitate patient compliance and convenience.
Comparison of ceftazidime concentrations in bile and serum
Authors: Bouza E , Hellín T , Rodríguez-Creixems M , Martínez-Beltrán J , Loza E , Baquero F
Published: June 2012

Biliary excretion of ceftazidime, a new broad-spectrum cephalosporin, was studied in two groups of patients after administration of a 2-g dose intravenously. Group A included 10 patients in whom ceftazidime levels in bile were measured during cholecystectomy. Group B included 10 patients with indwelling biliary tubes in whom ceftazidime levels in bile and serum were simultaneously measured at 0.5, 1, 2, 4, 6, and 8 h after administration of the drug. Although ceftazidime levels were variable, they exceeded the minimal inhibitory concentrations of most biliary tract pathogens in both groups.
Polycations sensitize enteric bacteria to antibiotics
Authors: Vaara M , Vaara T
Published: June 2012

Polymyxin B nonapeptide, a polymyxin B derivative which lacks the fatty acyl part and the bactericidal activity of polymyxin, was shown to sensitize smooth encapsulated Escherichia coli (O18:K1) and smooth Salmonella typhimurium to hydrophobic antibiotics (novobiocin, fusidic acid, erythromycin, clindamycin, nafcillin, and cloxacillin). The polymyxin B nonapeptide-treated bacteria were as sensitive to these antibiotics as are deep rough mutants. A lysine polymer with 20 lysine residues (lysine 20) had a largely similar effect. Larger lysine polymers and the protamine salmine were bactericidal but, at sublethal concentrations, sensitized the strains to the antibiotics mentioned above, whereas lysine4, streptomycin, cytochrome c, lysozyme, and the polyamines cadaverine, spermidine, and spermine had neither bactericidal nor sensitizing activity.
Polycations as outer membrane-disorganizing agents
Authors: Vaara M , Vaara T
Published: June 2012

The outer membrane-disorganizing effect of a short (10-min) treatment with polycationic agents was studied with smooth Salmonella typhimurium used as a test organism. The polycationic agents were the protamine salmine, a lysine polymer with 20 lysine residues (lysine20), and the deacylated polymyxin B derivative polymyxin B nonapeptide. Two different types of outer membrane-disorganizing were found. Protamine and lysine20 released 20 to 30% of the lipopolysaccharide from the outer membrane and sensitized the bacteria to the anionic detergent sodium dodecyl sulfate but did not (under these conditions) make the bacteria permeable to the hydrophobic probes fusidic acid and actinomycin D. In contrast, polymyxin B nonapeptide did not release lipopolysaccharide or sensitize the bacteria to sodium dodecyl sulfate but made the outer membrane permeable to the hydrophobic probes. None of the agents was bactericidal under the conditions used or caused any leakage of periplasmic beta-lactamase. Polymyxin B was used as a reference and showed characteristic outer membrane-disorganizing action. In thin-section electron microscopy, polymyxin B nonapeptide caused the appearance of long, narrow, finger-like projections on the outer membrane. Protamine and lysine20 caused a distinctly wrinkled appearance of the outer membrane but no projections.
Antibacterial activity of cefoperazone alone and in combination against cephalosporinase-producing Enterobacter cloacae
Authors: Minami S , Matsubara N , Yotsuji A , Watanabe Y , Yasuda T , Saikawa I , Mitsuhashi S
Published: June 2012

The activity of cefoperazone against a strain with an inducible cephalosporinase and a mutant that produces the enzyme constitutively indicates that the low inducer activity of this antibiotic plays an important role in its activity against Enterobacter cloacae.
Minimal inhibitory concentrations of lucknomycin, a new polyenic derivative, for Candida and Aspergillus spp
Authors: Martínez-Quesada J , Torres-Rodriguez J M , Rosés-Codinachs M , Amaral-Olivera M
Published: June 2012

The minimal inhibitory concentrations (MICs) of lucknomycin, a new polyenic derivative, were determined for 101 clinical isolates of Candida, 38 clinical or environmental strains of Aspergillus fumigatus, and 30 isolates of A. niger. The most susceptible species were Candida albicans and Candida tropicalis (mean MIC, 0.4 micrograms/ml). Aspergillus spp. were less susceptible, with mean MICs of 0.60 micrograms/ml for Aspergillus niger and 9.2 micrograms/ml for Aspergillus fumigatus.
Treatment of intracranial dengue virus infections in mice with a lipophilic derivative of ribavirin
Authors: Koff W C , Pratt R D , Elm J L , Venkateshan C N , Halstead S B
Published: June 2012

Rimantadine, ribavirin, and 6-mercapto-9-(tetrahydro-2-furyl)purine, administered intraperitoneally every 8 h for 7 days starting minutes after virus challenge, had no effect on survival and mean survival time of BALB/c mice inoculated intracranially with dengue virus type 2. In contrast, intraperitoneal treatment with ribavirin 2',3',5'-triacetate, a lipophilic analog of ribavirin, effected significant increases in both mean survival time and survival rate, suggesting that ribavirin 2',3',5'-triacetate may be superior to rabavirin for treatment of viral diseases of the brain.
Comparison of cefadroxil and cephalexin in the treatment of community-acquired pneumonia
Authors: Blaser M J , Klaus B D , Jacobson J A , Kasworm E , LaForce F M
Published: June 2012

Thirty-four patients with community-acquired acute pneumonias were treated in a prospective, randomized trial with either cefadroxil, 500 mg twice daily, or cephalexin, 250 mg four times daily. In both groups of patients, the presence of chronic illnesses predisposing to pneumonia was common. Streptococcus pneumoniae was isolated from 65% of the initial sputum specimens, and most illnesses were of mild to moderate severity. All 19 cases treated with cefadroxil and all 15 cases treated with cephalexin were clinically cured, and adverse reactions to the medications were minimal. The success of these regimens suggests that outpatient use of oral cephalosporin therapy may be an appropriate treatment of patients with mild or moderate community-acquired pneumonia.
Properties of IncP-2 plasmids of Pseudomonas spp
Authors: Jacoby G A , Sutton L , Knobel L , Mammen P
Published: June 2012

Thirty IncP-2 R plasmids from isolates of Pseudomonas spp. of diverse geographical origins were examined for the production of resistance properties. All the plasmids determined resistance to tellurite and all inhibited the propagation of certain DNA phages, although several patterns of phage inhibition were detected. Of the 30 plasmids, 29 determined resistance to streptomycin, 28 determined resistance to mercuric ion, and 24 determined resistance to sulfonamide. Resistance to other antibiotics, to compounds of arsenic, boron, or chromium, and to UV irradiation was less common. The degradative plasmid CAM also belonged to this group. When CAM was introduced into recipients carrying an IncP-2 R plasmid, recombinant plasmids were often formed in which antibiotic resistance and the ability to grow on camphor were transferred together to further recipients or were lost together in a strain in which IncP-2 plasmids were unstable. Such hybrid plasmid formation was rec dependent. CAM and other IncP-2 plasmids that determine UV light resistance demonstrated UV-enhanced, nonpolarized transfer of the Pseudomonas aeruginosa chromosome. By agarose gel electrophoresis, all IncP-2 R plasmids and CAM were ca. 300 X 10(6) in molecular weight.
Use of ceftazidime in the therapy of serious infections, including those due to multiresistant organisms
Authors: Clumeck N , Van Laethem Y , Gordts B , Jaspar N , Butzler J P
Published: June 2012

Ceftazidime was administered intravenously or intramuscularly or both in doses of 1 to 6 g per day to 33 patients with serious gram-negative bacillary infections (12 pulmonary, 10 urinary tract, 4 soft tissue, 4 intraabdominal, and 3 miscellaneous infections). Twenty-one patients were septicemic. We identified 20 isolates of members of the family Enterobacteriaceae and 13 isolates of Pseudomonas aeruginosa. Seventeen patients had failed to respond to previous antimicrobial therapy. A total of 23 patients were clinically cured, 7 patients improved, and 3 patients failed to respond to therapy. The selection or emergence of resistant organisms during treatment (mostly Candida spp., Staphylococcus aureus, and enterococci) was noted in 11 patients. Toxicity was minimal (reversible mild liver function abnormalities and eosinophilia). The results of this study suggest that ceftazidime is an effective and well-tolerated new cephalosporin for the therapy of serious infections due to susceptible gram-negative organisms.
Relative activities of acyclovir and BW759 against Aujeszky's disease and equine rhinopneumonitis viruses
Authors: Rollinson E A , White G
Published: June 2012

Compound BW759 (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine) was shown to be about 230 times more active than acyclovir (9-[2-hydroxyethoxymethyl]guanine) (ACV) against Equid herpesvirus type 1 infection in Syrian hamsters and was more effective against Aujeszky's disease in mice. The therapeutic superiority of BW759 over ACV was greater than expected from quantitative inhibitory results in tissue culture with these viruses. When administered to hamsters at dose rates sufficient to prevent any Equid herpesvirus type 1-induced mortality (100 mg of ACV per kg per day; 3 mg of BW759 per kg per day), BW759 inhibited viral multiplication, as judged by histopathological observations, clinical chemistry, and liver virus concentrations, to a greater extent than ACV. Compound BW759 was particularly effective when administered via the oral route. The reasons for the superiority of BW759 over ACV remain to be elucidated.
Pharmacokinetics of aztreonam in patients with various degrees of renal dysfunction
Authors: Mihindu J C , Scheld W M , Bolton N D , Spyker D A , Swabb E A , Bolton W K
Published: June 2012

We have studied the pharmacokinetics of 1-g intravenous doses of aztreonam in four groups of six volunteers each, distinguished by their creatinine clearances (greater than 80, 30 to 80, 10 to 29, and less than 10 ml/min). Subjects received 1 g of aztreonam intravenously without any complications. Aztreonam serum and urine levels were measured by microbiological methods and by high-pressure liquid chromatography, and unbound serum aztreonam was determined by ultrafiltration. Serum levels were well described by a two-compartment infusion model. From this model we determined steady-state volume of distribution, alpha distribution phase half-life, beta elimination phase half-life, and total clearance of aztreonam. The mean of beta elimination phase half-life ranged from 2 h in normal subjects to 6 h in anephric patients. The total clearance of aztreonam correlated closely with corrected creatinine clearance calculated from serum creatinine, age, and sex (r = 0.97, P less than 0.001) and ranged from a mean value of 107 ml/min in normal subjects to 29 ml/min in functionally anephric patients. Some 75% of aztreonam excretion was renal. Urinary recovery of aztreonam ranged from 58% of the administered dose in normal subjects to 1.4% in uremic patients. Free aztreonam in serum correlated inversely with creatinine clearance (P less than 0.001). A nomogram was developed as a guide for adjustment of aztreonam dosage according to renal function.
Intermittent chemoprophylaxis for Pneumocystis carinii pneumonia
Authors: Hughes W T , Smith B L
Published: June 2012

An intermittent regimen of trimethoprim-sulfamethoxazole was tested in the corticosteroid-treated rat model to learn whether or not administration for 3 consecutive days a week would provide prophylaxis equal to continuous daily doses. Although all of the untreated control animals acquired Pneumocystis carinii pneumonia, none of the animals given either continuous or intermittent trimethoprim-sulfamethoxazole became infected.
In vitro activity of ceftriaxone alone and in combination with gentamicin, tobramycin, and amikacin against Pseudomonas aeruginosa
Authors: Watanakunakorn C
Published: June 2012

The in vitro activity of ceftriaxone alone and in combination with gentamicin, tobramycin, and amikacin against 50 Pseudomonas aeruginosa strains was studied by the broth dilution method and the time-kill curve method. The majority of the P. aeruginosa strains tested were resistant to ceftriaxone. Combining ceftriaxone with the aminoglycosides resulted in synergism, antagonism, or indifference.
Effect of mannitol infusions into the internal carotid artery on entry of two antibiotics into the cerebrospinal fluid and brains of normal rabbits
Authors: Perkins B A , Strausbaugh L J
Published: June 2012

The rapid infusion of hyperosmolar solutions into the internal carotid artery transiently disrupts the integrity of the blood-brain barrier, permitting entry of substances normally excluded from the nervous system. This study examined the effect of such an infusion on the penetration of vancomycin and tobramycin into the cerebrospinal fluid and brains of normal rabbits. Groups of five to seven animals were assigned either to control groups, receiving vancomycin or tobramycin alone, or to experimental groups, receiving these antibiotics with 40-s intracarotid infusions of 8.0 ml of 25% mannitol. Serum, cerebrospinal fluid, and brain specimens were obtained for assay 135 min after dosage. Concentrations of these antibiotics in serum were comparable in control and experimental groups; concentrations of the antibiotics in cerebrospinal fluid were significantly higher in the experimental groups. Mean (+/- standard deviation) concentrations of the antibiotics in cerebrospinal fluid were, respectively, less than 0.5 and 4.1 +/- 4.6 micrograms of vancomycin per ml and 0.6 +/- 0.5 and 3.4 +/- 2.4 micrograms of tobramycin per ml in the control and experimental groups. The concentrations of these antibiotics in brains were also higher in the experimental groups. This trend achieved statistical significance in the tobramycin studies, where control animals uniformly had tobramycin concentrations in brains of less than 0.1 microgram/g and experimental group animals had a mean concentration of 0.4 microgram/g. Additional studies with tobramycin indicated that intracarotid antibiotic administration immediately after the mannitol infusion further augmented antibiotic concentrations in brains.