bluuebunny/crossref_metadata_2025 huggingface dataset:
beta-Lactam resistance in Serratia marcescens: comparison of action of benzylpenicillin, Apalcillin, Cefazolin, and ceftizoxime
Authors: Takata N , Suginaka H , Kotani S , Ogawa M , Kosaki G
Published: June 2012

The intrinsic mechanisms of resistance to beta-lactam antibiotics in Serratia marcescens IFO 12648 were investigated, comparing the action of benzylpenicillin, apalcillin, cefazolin, and ceftizoxime. The minimal inhibitory concentrations for this strain were 1,600, 3.13, 6,400, and 0.05 microgram/ml, respectively. The addition of ethylenediaminetetraacetic acid markedly reduced the minimal inhibitory concentrations of benzylpenicillin and cefazolin, whereas those of apalcillin and ceftizoxime were not influenced. S. marcescens IFO 12648 produced only a low level of beta-lactamase activity constitutively, and the production was considerably increased by the addition of benzylpenicillin. Cefazolin was hydrolyzed rapidly by beta-lactamase activity, whereas benzylpenicillin, apalcillin, and ceftizoxime were poorly hydrolyzed. Peptidoglycan synthesis in ether-treated strain IFO 12646 cells was inhibited by a concentration of ceftizoxime markedly lower than that of cefazolin and by a concentration of apalcillin moderately lower than that of benzylpenicillin.
Nifurzide, a nitrofuran antiinfectious agent: interaction with Escherichia coli cells
Authors: Delsarte A , Faway M , Frère J M , Coyette J , Calberg-Bacq C M , Heinen E
Published: June 2012

This paper presents a study of the interactions between Escherichia coli cells and nifurzide, a nitrofuran derivative which is used as an intestinal antiinfectious agent. At low concentrations of nifurzide, the growth rate of the cultures decreased, and elongated, nonseptate cells appeared. At high concentrations, complete growth inhibition occurred, accompanied by a rather strong bactericidal effect, but the appearance of the cells was normal; in particular, no bacteriolytic effect was observed. A very large number of antibiotic molecules were bound per bacterial cell. After cell disruption, similar amounts of nifurzide were found in the cytoplasm, cytoplasmic membranes, and cell wall, respectively. Most of the bound nifurzide was rapidly degraded or became protein bound. The structure of the outer membrane lipopolysaccharide appeared to have little influence on the activity of nifurzide.
In vitro comparison of third-generation cephalosporins, piperacillin, dibekacin, and other aminoglycosides against aerobic bacteria
Authors: Pulliam L , Hadley W K , Mills J
Published: June 2012

The in vitro activities of four new beta-lactam antibiotics and dibekacin against aerobic bacteria were compared. The new cephalosporins were more broadly active against gram-negative bacteria than were presently available cephalosporins, but were less active against staphylococci.
Comparison of five methods for the assay of serum gentamicin
Authors: Ratcliff R M , Mirelli C , Moran E , O'Leary D , White R
Published: June 2012

The microbiological bioassay, the adenylation method, and the radiometric, enzyme, and fluorescent immunoassay methods for assaying serum gentamicin were compared. The precision, reproducibility, and specificity of each method was assessed and proved satisfactory, with the exception of the radioimmunoassay, which gave artificially high results. Good correlations between the other four methods was obtained in a comparison involving 103 patient sera. The other aspects of performance were also compared, namely, simplicity, speed, cost, ease of automation, and application to large and small workloads. The enzyme immunoassay performed best in this comparison, being accurate, specific, rapid, and very simple to perform. However, other laboratories might find that workload, staffing, and available equipment make other methods more attractive.
Mecillinam Susceptibility of
Escherichia coli
K-12 Mutants Deficient in the Adenosine 3′,5′-Monophosphate System
Authors: Scott Nigel W. , Harwood Colin R.
Published: June 2012

The mecillinam resistance of
Escherichia coli
K-12 mutants deficient in the enzyme responsible for the synthesis of adenosine 3′,5′-monophosphate, adenylate cyclase, has been investigated. The results suggest that resistance to this antibiotic may be a consequence of the slow growth rate of these mutants rather than an intrinsic property of their genetic lesion.
Isoelectric focusing of Bacteroides melaninogenicus group beta-lactamases
Authors: Timewell R M , Phillips I , Söderholm J , Nord C E
Published: June 2012

beta-Lactamases extracted by sonication from the Bacteroides melaninogenicus group organisms (B. asaccharolyticus, B. melaninogenicus, B. bivius, and B. oralis) were found to be in the form of complexes with molecular weights of greater than or equal to 40 x 10(6), and this resulted in failure to characterize them by isoelectric focusing. Purification by el filtration in the presence of deoxycholate resulted in beta-lactamase preparations from B. bivius with pI's of 5.7. A beta-lactamase preparation extracted by osmotic shock from B. bivius also had a pI of 5.7. Osmotic shock preparations from B. asaccharolyticus, B. melaninogenicus, and B. oralis had two bands of equal intensity with pI's of 4.2 and 4.35.
Activity of moxalactam and cefotaxime alone and in combination with ampicillin or penicillin against group B streptococci
Authors: Landesman S H , Corrado M L , Cherubin C E , Sierra M F
Published: June 2012

The activities of moxalactam and cefotaxime, alone and combined with ampicillin or penicillin, against 40 isolates of group B streptococci were assessed by using the microtiter broth dilution, checkerboard, and time-kill techniques. Penicillin and cefotaxime were bactericidal for all isolates at concentrations of 0.06 micrograms/ml or less. Ampicillin was slightly less active. Moxalactam was bactericidal for all strains at concentrations of 4 to 8 micrograms/ml. The ampicillin- moxalactam combination was partially synergistic for 60% of the isolates tested; the ampicillin-cefotaxime combination was partially synergistic for 35% of these isolates. No instances of antagonism were observed. In time-kill evaluations, ampicillin (3.0 micrograms/ml) and penicillin (0.75 micrograms/ml) effected 2.5 to 3.5 log10 reductions in numbers of colony-forming units. The addition of 4 micrograms of cefotaxime per ml or 8 to 16 micrograms of moxalactam per ml to penicillin or ampicillin did not alter killing kinetics. Moxalactam and cefotaxime neither enhanced nor decreased the activity of ampicillin or penicillin against group B streptococci.
Transmissible plasmids from Campylobacter jejuni
Authors: Taylor D E , De Grandis S A , Karmali M A , Fleming P C
Published: June 2012

Tetracycline resistance in clinical isolates of Campylobacter jejuni was shown to be plasmid mediated. Intra- and interspecies transfers to C. fetus subsp. fetus were demonstrated. The frequency of transfer was increased by approximately 100-fold on a solid surface by using a plate- or filter-mating procedure, as compared with a liquid-mating method. Results of experiments in which cell-free filtrates were used to replace the donor strain in mating experiments tend to rule out bacteriophage-mediated transduction in the transfer of tetracycline resistance. The plasmid-transfer frequency was not affected when deoxyribonuclease was added to the agar used in the mating experiments, indicating that transformation was not involved. Four transmissible plasmids from different tetracycline-resistant strains of C. jejuni each had a molecular weight of 38 x 10(6). Transfer of these plasmids to Escherichia coli was not demonstrated.
Selective Inhibition of Herpesvirus Deoxyribonucleic Acid Synthesis by Acycloguanosine, 2′-Fluoro-5-Iodo-Aracytosine, and (
E
)-5-(2-Bromovinyl)-2′-Deoxyuridine
Authors: Larsson A. , Öberg B.
Published: June 2012

The selectivity of inhibition of herpesvirus deoxyribonucleic acid synthesis by acycloguanosine, 2′-fluoro-5-iodo-aracytosine, and (
E
)-5-(2-bromovinyl)-2′-deoxyuridine was determined by isopycnic banding of
32
P-labeled deoxyribonucleic acid from herpesvirus-infected and uninfected cells.
Human pharmacokinetics and disposition of sarmoxicillin, a lipophilic amoxicillin prodrug
Authors: Smyth R D , Pfeffer M , Van Harken D R , Cohen A , Hottendorf G H
Published: June 2012

Sarmoxicillin, an amoxicillin prodrug, is the methoxymethyl ester of hetamoxicillin. Esterification converted amoxicillin from an amphoteric to a cationic compound and resulted in a 30- to 600-fold increase in lipid partitioning. Oral absorption studies in normal subjects demonstrated that sarmoxicillin was only partially hydrolyzed by nonenzymatic and gut or hepatic first-pass metabolism and that significant quantities of intact ester appeared in the systemic circulation. Sarmoxicillin was converted to amoxicillin in plasma by hydrolysis of the acetone penicinate and the methoxymethyl ester bonds. Significant amoxicillin levels were demonstrated in saliva after administration of sarmoxicillin, but not amoxicillin, over a 250- to 1,000-mg dose range. Differences in the absorption, distribution, or metabolism of amoxicillin were also evident in the lower plasma amoxicillin maximum concentration and area under the curve and longer half-life after sarmoxicillin administration. Differences in the distribution of this lipophilic ester could result in a significant increase in tissue penetration and subsequent therapeutic efficacy of amoxicillin when administered as sarmoxicillin.
Pharmacokinetics of netilmicin in children with and without cystic fibrosis
Authors: Michalsen H , Bergan T
Published: June 2012

The pharmacokinetics of intravenous netilmicin was studied in cystic fibrosis (CF) and non-CF patients who were closely matched according to age. The serum concentrations showed a moderately higher variance within the CF group. The serum half-life in CF patients was 1.37 h compared with 2.29 h in the non-CF subjects (P less than 0.05). The apparent distribution coefficients were 0.306 and 0.356 liters/kg in the CF and non-CF groups, respectively. The mean body clearance was 6.6 liters/h per 1.73 m2 in the CF group compared with 5.3 liters/h per m2 in the non-CF controls, but the difference was not significant. The mean renal clearance in CF patients was 4.7 liters/h per 1.73 m2. From a pharmacokinetic point of view, the dosage of netilmicin required may be the same in CF as in non-CF patients.
Heterogeneity of antibiotic resistance in mucoid isolates of Pseudomonas aeruginosa obtained from cystic fibrosis patients: role of outer membrane proteins
Authors: Irvin R T , Govan J W , Fyfe J A , Costerton J W
Published: June 2012

Mucoid Pseudomonas aeruginosa strains isolated from cystic fibrosis patients are very heterogeneous and include a class which is hypersusceptible to carbenicillin (minimum inhibitory concentration, less than or equal to 1 microgram/ml). Hypersusceptible mucoid P. aeruginosa isolates were found in 12 of 22 cystic fibrosis patients examined. In cystic fibrosis patients having both resistant and hypersusceptible mucoid strains, 24 of 54 mucoid colonies obtained from a sputum sample were found to belong to the hypersusceptible class. In most instances, hypersusceptible and resistant strains isolated from the same sputum sample were indistinguishable, aside from their antibiotic susceptibilities, by classical methods. A particular pair of mucoid isolates (one hypersusceptible and one resistant) was chosen for further study. The hypersusceptibility was not limited to carbenicillin but was found to extend to other penicillins, tetracycline, and trimethoprim but not to the aminoglycosides gentamicin and tobramycin. The hypersusceptibility of the mucoid strain was found to be unrelated to amount or ability to synthesize alginate. The hypersusceptible strain was found to have two additional outer membrane proteins (32,000 and 25,000 daltons) as compared with the resistant strain. The 32,000-dalton protein, termed protein N1, was found to be correlated to the hypersusceptibility phenotype, as all spontaneous mutants of the hypersusceptible mucoid strain which were capable of growing in the presence of 50 microgram of carbenicillin per ml had lost the 32,000-dalton outer membrane protein. The possible origins of the hypersusceptibility phenotype and the implications of the heterogeneity of mucoid P. aeruginosa in the pathogenesis of P. aeruginosa are discussed.
Serum Aminoglycoside Assay by Enzyme-Mediated Immunoassay (EMIT): Correlation with Radioimmunoassay, Fluoroimmunoassay, and Acetyltransferase and Microbiological Assays
Authors: White L. O. , Scammell L. M. , Reeves D. S.
Published: June 2012

Enzyme-mediated immunoassay (EMIT) serum aminoglycoside assay results were accurate and precise and correlated well with radioimmunoassay, fluoroimmunoassay, and acetyltransferase and microbiological assay determinations.
In vitro and in vivo synergism between amoxicillin and clavulanic acid against ampicillin-resistant Haemophilus influenzae type b
Authors: Yogev R , Melick C , Kabat W J
Published: June 2012

Eight strans of ampicillin-resistant beta-lactamase-producing Haemophilus influenzae type b were studied in vitro for synergy between amoxicillin and clavulanic acid. The minimal inhibitory concentrations for amoxicillin alone were 6.25 to 12.5 microgram/ml, and for clavulanic acid alone they were 12.5 to 25 microgram/ml. However, seven of eight strains were inhibited by a combination of 0.36 microgram of amoxicillin and 0.36 microgram of clavulanic acid per ml. Infant rat models of bacteremia and meningitis were used to test the efficacy of amoxicillin and clavulanic acid alone and in combination upon four strains of ampicillin-resistant H. influenzae. Neither amoxicillin alone (27 animals) nor clavulanic acid alone (20 animals) sterilized the blood or cerebrospinal fluid of the animals. In contrast, 30 of 33 blood cultures and 29 of 33 cerebrospinal fluid cultures were sterile when a combination of the two drugs in the same dosages was used. The observed in vitro and in vivo synergism between amoxicillin and clavulanic acid suggests that the combination may be effective therapy for invasive infections in humans caused by ampicillin-resistant H. influenzae type b.
Absence of Tolerance to Cefoxitin in Anaerobic Bacteria
Authors: Goldstein Ellie J. C. , Kwok Y. Y. , Sutter Vera L.
Published: June 2012

None of the 46 strains of anaerobic bacteria tested, including 26 strains of
Bacteroides fragilis
, showed tolerance (minimal bactericidal concentration/minimum inhibitory concentration ratio >32) to cefoxitin.
Effect of antimicrobial agents on human polymorphonuclear leukocyte microbicidal function
Authors: Welch W D , Davis D , Thrupp L D
Published: June 2012

The effect of 19 antimicrobial agents on human polymorphonuclear leukocyte function was evaluated by chemiluminescence assays, yeast phagocytosis and killing, and lactate dehydrogenase release. Tetracycline and trimethoprim inhibited chemiluminescence and reduced killing at therapeutic concentrations of 2 microgram/ml. Cephalothin inhibited yeast killing at a concentration of 20 microgram/ml, but a significant depression of polymorphonuclear leukocyte chemiluminescence was encountered only at higher levels of 200 microgram/ml. The inhibition shown by these drugs was reversible. None of the other antimicrobial agents tested demonstrated inhibition of chemiluminescence, phagocytosis, or killing at usual clinical serum levels. No antimicrobial agent tested caused release of lactate dehydrogenase from polymorphonuclear leukocytes. The results suggest that therapeutic concentrations of tetracycline, trimethoprim, and cephalothin may inhibit optimal polymorphonuclear leukocyte microbicidal function.
Physiological response of Saccharomyces cerevisiae to 15-azasterol-mediated growth inhibition
Authors: Rodriguez R J , Parks L W
Published: June 2012

We studied 15-aza-24-methylene-8,14-cholestadiene-3 beta-ol (15-azasterol) inhibition of Saccharomyces cerevisiae growth. Exposure to sublethal concentrations of this drug caused S. cerevisiae cells to undergo a transient period of inhibition at midlog phase. During growth inhibition the turbidity of each culture remained constant, as did the total cell number. Although the proportion of viable cells in cultures decreased from 90 to 12% during inhibition, methylene blue staining showed that less than 40% of the cells underwent metabolic inactivation. We monitored adenosine triphosphate levels throughout the inhibition cycle, and these levels followed kinetics identical to cell growth kinetics. After overcoming inhibition, cellular lipid extracts revealed the presence of a modified form of 15-azasterol. It appeared that the yeast cells were able to overcome 15-azasterol inhibition by an inactivating transmethylation reaction involving S-adenosylmethionine.
Penicillin tolerance of human isolates of group C streptococci
Authors: Portnoy D , Prentis J , Richards G K
Published: June 2012

Seventeen clinical isolates of group C streptococci were tested for penicillin tolerance. Sixteen of the strains showed penicillin tolerance with a 32-fold or greater difference between the minimal inhibitory concentration and the minimal bactericidal concentration. Synergism was demonstrated with a combination of penicillin and gentamicin for all 17 strains tested. The rate of antibiotic killing was measured for five of the streptococcal strains by using the combination of penicillin and gentamicin. All isolates were killed within 5 h with the combination, but viable organisms were recovered after 48 h when either drug was used alone. Our study suggests that penicillin tolerance with group C streptococci may occur frequently and may account for the poor outcome of serious group C streptococcal infections tested with penicillin alone.
Determination of moxalactam in human body fluids by liquid chromatographic and microbiological methods
Authors: Miner D J , Coleman D L , Shepherd A M , Hardin T C
Published: June 2012

High-performance liquid chromatographic methods for determination of the isomers of moxalactam in plasma and urine have been developed. Conventional reverse-phase chromatography was used for plasma assays, and an ion-pairing reagent was included for urine assays. Detection limits were 1.5 micrograms/ml of plasma and 7.5 micrograms/ml of urine. The high-performance liquid chromatographic assays were extensively compared with a microbiological assay (detection limit, 1 microgram/ml), using samples from human volunteers to whom moxalactam had been administered as well as plasma and urine from untreated humans, to which moxalactam was added. The correlations between the assays were quite good, but the precision and accuracy of the high-performance liquid chromatographic methods were superior. Both types of assays were used in a study of the stability of moxalactam-containing samples at various temperatures.
Curative effects of tobramycin or gentamicin therapy on mouse arthritis caused by Mycoplasma pulmonis
Authors: Dixon R A
Published: June 2012

Inbred mice infected intravenously with Mycoplasma pulmonis develop a severe and persistent arthritis. Maximal severity of the arthritis is reached 10 to 14 days postinfection, and in some animals, ian arthritic condition subsequently persists throughout life. Chemotherapy was given either at the time of infection or during the acute phase of the disease. Tobramycin, gentamicin, and, to a lesser extent, kanamycin delayed the development of arthritis when administered at the time of infection, and, when given therapeutically, they all reduced inflammation and swelling of arthritic joints. Recovery of the mycoplasma was lowest from the joints of more treated with tobramycin or gentamicin, indicating that these two antibiotics were mycoplasmacidal and that the remission of arthritis was correlated with the eradication of the organisms.
In vitro activity of ceftizoxime against Bacteroides fragilis: comparison with benzylpenicillin, cephalothin, and cefoxitin
Authors: Eley A , Greenwood D
Published: June 2012

Minimum inhibitory concentrations of ceftizoxime for seven clinical isolates of Bacteroides fragilis were found to be markedly affected by inoculum size; the very low minimum inhibitory concentration values (less than or equal to 0.25 microgram/ml) obtained in tests with most strains were not sustained when the inoculum was raised 100-fold. Benzylpenicillin and cephalothin were also affected by inoculum size, but cefoxitin was not. Antibiotic assays showed that the strains inactivated ceftizoxime and cephalothin completely, benzylpenicillin partially, and cefoxitin not at all. Morphological investigations revealed that populations of B. fragilis responded differently to each of the four beta-lactam agents during the early stages of the encounter between B. fragilis and the antibiotic. Benzylpenicillin and cefoxitin induced spheroplast formation at lower concentrations than did ceftizoxime. Cephalothin evoked a novel morphological response that was not seen with other beta-lactam agents.
Properties of S-adenosyl-L-methionine:macrocin O-methyltransferase in extracts of Streptomyces fradiae strains which produce normal or elevated levels of tylosin and in mutants blocked in specific O-methylations
Authors: Seno E T , Baltz R H
Published: June 2012

An efficient assay for S-adenosyl-L-methionine:macrocin O-methyltransferase, the enzyme which carries out the terminal step in tylosin biosynthesis, is described. Macrocin O-methyltransferase requires Mg2+ and S-adenosyl-L-methionine for activity, has a temperature optimum of about 31 degrees C, and has a pH optimum of 7.5 to 8.2. Macrocin O-methyltransferase specifically converts macrocin to tylosin by O-methylation of the 3" ' position of macrocin. In vitro methylation studies with extracts from a tylosin-producing Streptomyces fradiae strain and from mutant strains blocked in 2" '- or 3" '-O-methylations indicated that: (i) the 2" '- and 3" '-O-methylations occur after 6-deoxy-D-allose is attached to the macrolide ring; (ii) the 2" '- and 3" '-O-methylations are carried out by separate enzymes; and (iii) the 2" '-O-methylation precedes the 3" '-O-methylation. Macrocin O-methyltransferase was inhibited by high levels of its substrate, macrocin, by its product, tylosin, and by other tylosin analogs which contained mycinose or demethyl analogs of mycinose. Macrocin O-methyltransferase was produced early in the tylosin fermentation cycle by S. fradiae and preceded the onset of rapid tylosin biosynthesis by about 24 h. The enzyme specific activity reached maximum at about 72 h and then slowly declined. A mutant strain of S. fradiae selected for increased tylosin production synthesized macrocin O-methyltransferase more rapidly and accumulated a higher enzyme specific activity than a wild-type strain.
Gentamicin pharmacokinetic changes in induced acute canine nephrotoxic glomerulonephritis
Authors: Riviere J E , Coppoc G L , Hinsman E J , Carlton W W
Published: June 2012

Most clinical schemes used to adjust gentamicin dosage regimens in renal insufficiency assume that the volume of distribution remains constant. The purpose of this investigation was to determine the pharmacokinetic parameters of gentamicin (two-compartment open model) before and at two points during the acute phase of experimentally induced nephrotoxic (injection of anti-glomerular basement membrane antibody) glomerulonephritis in beagle dogs. Disease was verified by decreased 24-h creatinine clearance, increased 24-h urinary protein excretion, and characteristic immunofluorescent, light- and electron-microscopic lesions. After disease induction, the concentration of drug in serum at time zero (Cp0) was significantly decreased and the volume of the central compartment (Vc) and the volume of distribution (Vd(area)) were increased in all treated dogs. These findings suggest that the assumption of unchanged volume of distribution in acute glomerulonephritis could lead to a serious overestimation of serum drug concentration.
Pharmacokinetics of moxalactam in patients with renal failure and during hemodialysis
Authors: Srinivasan S , Neu H C
Published: June 2012

The pharmacokinetics of moxalactam were determined in eight patients with end stage renal disease who were undergoing chronic hemodialysis. The mean half-life of moxalactam in the interdialysis period was 19 h, with a range of 9 to 30 h. The mean half-life of moxalactam during dialysis was 4 +/- 0.58 h. Serum levels of 30 +/- 10 micrograms/ml were present 24 h after a 1-g dose in the interdialysis period. A dose of 1 g at the end of each dialysis period in patients undergoing thrice-weekly hemodialysis would provide levels far in excess of the minimal inhibitory levels against Enterobacteriaceae.
Metronidazole Metabolism in Cultures of
Entamoeba histolytica
and
Trichomonas vaginalis
Authors: Beaulieu Bernard B. , McLafferty Martha A. , Koch Ronald L. , Goldman Peter
Published: June 2012

Acetamide forms from metronidazole in cultures of either
Entamoeba histolytica
or
Trichomonas vaginalis
as it does in cultures of bacteria which are susceptible to this drug. Under aerobic conditions, the formation of acetamide is more rapid in a strain of
T. vaginalis
which is more susceptible to metronidazole. Thus, it appears that the formation of acetamide may be associated with the microbiocidal action of metronidazole.
Rifampin, ampicillin, streptomycin, and their combinations in the treatment of enterococcal pyelonephritis in rats
Authors: Oill P A , Kalmanson G M , Guze L B
Published: June 2012

The activities of ampicillin, rifampin, streptomycin, and their combinations were evaluated in vitro against Streptococcus faecalis strain GK and in vivo in rats with an established pyelonephritis resulting from challenge with this same enterococcus. In vitro synergy was demonstrated between all combinations. Comparison of the log colony-forming units of S. faecalis recovered per gram of kidney tissue showed that all treated groups had significant lower numbers than controls (P less than 0.001). Ampicillin plus streptomycin or ampicillin alone was superior to rifampin alone or rifampin plus streptomycin at each interval (P less than 0.001). There was no significant difference between ampicillin and rifampin plus ampicillin. The disparity between in vitro and in vivo results again raises some doubts as to the relevance of in vitro observations to clinical outcome.
Spread of R-plasmids among Escherichia coli causing urinary tract infections
Authors: Hughes C , Bauer E , Roberts A P
Published: June 2012

The incidence of multiple-antibiotic resistance among Escherichia coli isolated from urinary tract infections at Charing Cross Hospital, London, increased over the last 10 years, and its distribution was related to O-type. Among strains of the eight O-types most frequently causing such infections at this hospital, O4, O9, and O18 had a high incidence of multiple resistance (35, 22, and 19%, respectively); O2 and O6 had a intermediate incidence (14 and 11%, respectively); and O7, O1, and O75 had a low incidence (8, 6, and less than 3%, respectively). This nonrandom distribution appears to be a consequence of unequal plasmid recipient ability. After overnight mating with antibiotic-resistant donors, R-plasmid infection frequencies among antibiotic-sensitive urinary tract isolates differed by up to 10(5)-fold, and such differences were correlated with the variation in the incidence of antibiotic resistance among the O-types. The inherent differences in the ability to achieve significant R-plasmid spread, which appear to be determined by the host, not the plasmid, may be compounded in some cases by the inhibition of potential mating partners by colicin production.
Bacteriocin and Hemolysin from
Streptococcus faecium
Authors: Nakagawa Shizutoshi , Matsuo Yoshiyasu
Published: June 2012

The bacteriocin and hemolysin produced by a
Streptococcus faecium
strain were partially separated after gel filtration on Ultrogel AcA-22. The molecular weight of bacteriocin was approximately 300,000, and that of hemolysin was 220,000. Non-bacteriocinogenic mutants retained the hemolytic activity. Production of hemolysin required glucose, whereas that of bacteriocin did not.
Penetration of moxalactam into its target proteins in Escherichia coli K-12: comparison of a highly moxalactam resistant mutant with its parent strain
Authors: Komatsu Y , Murakami K , Nishikawa T
Published: June 2012

An eschericia coli K-12 mutant highly resistant to moxalactam but only slightly resistant to other beta-lactam antibiotics was obtained by mutagen treatment. The affinity of moxalactam for its target penicillin-binding proteins was unchanged, as was the level of beta-lactamase activity. The penetration of [14C] moxalactam, however, was markedly reduced in the mutant. Electrophoretic analysis revealed alterations of the outer membrane proteins. A reduction in the amount of one of the pore-forming proteins (porins) was especially noteworthy. These data suggest that moxalactam resistance is the result of an alteration in the outer membrane structure.
Selective suppression of alimentary tract microbial flora as prophylaxis during granulocytopenia
Authors: Hargadon M T , Young V M , Schimpff S C , Wade J C , Minah G E
Published: June 2012

Oral nonabsorbable antibiotics have been used to suppress the rectal flora in granulocytopenic patients. Problems with these therapies, i.e., compliance, acquisition of undesirable flora, and cost, motivated the search for an alternative therapy which would increase compliance and effectively reduce the Enterobacteriaceae without creating a microbiol vacuum. Trimethoprim-sulfamethoxazole was found to be easily taken, to suppress the Enterobacteriaceae, and to maintain the anaerobic rectal flora for biological stability of the rectal ecosystem. However, concurrent use of parenteral antibiotics profoundly influenced rectal flora and temporarily destroyed the colonization resistance afforded by the anaerobes.
Treatment of uncomplicated gonorrhea with rosoxacin
Authors: Handsfield H H , Judson F N , Holmes K K
Published: June 2012

In a randomized, double-blind, dose-ranging study, single oral doses of rosoxacin were used to treat 126 patients with uncomplicated genital or anorectal gonorrhea. Neisseria gonorrhoeae was eradicated from 5 (28%) of 18 men treated with 100 mg, compared with 101 (94%) of 108 men and women treated with 200 mg, 300 mg, or 400 mg (P less than 0.001). Susceptibility to rosoxacin was determined for 6 pretreatment gonococcal isolates from these patients and for 194 stored clinical isolates; 296 (98.7%) of these 300 isolates, including 10 strains of penicillinase-producing N. gonorrhaeae, required a minimal inhibitory concentration of less than or equal to 0.062 microgram/ml. Urethral or cervical infection with Chlamydia trachomatis coexisted with gonococcal infection in 14 (22%) of 63 patients and persisted in 7 of 10 patients treated with rosoxacin. Postgonococcal urethritis developed in 11 (34%) of 32 men who were monitored for 12 to 30 days. Sixty-four subjects (51%) developed transient dizziness, drowsiness, altered visual perceptions, or other symptoms suggestive of central nervous system dysfunction after treatment with rosoxacin, but these symptoms were not clearly dose related. Rosoxacin in doses of greater than or equal to 200 mg appears to be effective for single-dose treatment of uncomplicated gonorrhea, but further studies of its possible central nervous system toxicity are indicated.
Ceforanide and cefazolin therapy of pneumonia: comparative clinical trial
Authors: Wallace R J , Martin R R , Quinones F J , Greenberg S B
Published: June 2012

Ceforanide is a new (parenteral) long-acting cephalosporin with antimicrobial activity comparable to those of other second-generation cephalosporins. In a randomized prospective study, patients with community-acquired bacterial pneumonia were treated with ceforanide at 0.5 g every 12 h (28 cases) or with cefazolin at 1.0 g every 8 h (26 cases). The study groups were comparable in clinical and laboratory findings, including etiological diagnosis. Streptococcus pneumoniae was isolated from the sputum of 38 patients, of whom 8 (21%) were bacteremic. Mean peak and trough serum levels of ceforanide drawn 1 and 11.5 h after the 0.5-g intravenous dose were 39.6 and 2.5 microgram/ml, respectively. Of the 50 patients evaluable for efficacy, all responded clinically with no serious adverse reactions. In spite of clinical improvement and in vitro susceptibility, Haemophilus influenzae persisted in the sputum of five of the eight cefazolin-treated patients and four of the five patients treated with ceforanide. Ceforanide appears to be as safe and effective as cefazolin for the therapy of pneumonia caused by S. pneumoniae or H. influenzae, but neither drug was effective in clearing H. influenzae from the sputum.
Multiple drug resistance in Mycobacterium avium: is the wall architecture responsible for exclusion of antimicrobial agents?
Authors: Rastogi N , Frehel C , Ryter A , Ohayon H , Lesourd M , David H L
Published: June 2012

Whole cells of Mycobacterium avium, characterized by their negative response in the nine biochemical tests used for mycobacterial identification in our laboratory, turned positive for nitrate reductase, Tween-80 hydrolysis, beta-glucosidase, acid phosphatase, alkaline phosphatase, penicillinase, and trehalase after their wall portion was removed to yield spheroplasts. This suggested that the negative results in most of the biochemical procedures were caused by the exclusion mechanism at the wall level. Preliminary transmission and scanning electron microscopic studies showed differences at wall level between laboratory-maintained opaque, dome-shaped (SmD) and host-recycled smooth, transparent (SmT) colony type variants of M. avium and suggested the presence of an outer regularly structured layer in SmT variants. Comparative ultrastructural studies utilizing different polysaccharide coloration methods confirmed the presence of an outer polysaccharide layer in SmT variants which was probably related to their enhanced pathogenicity for experimental animals and drug resistance as compared to that of SmD variants. These findings are discussed with respect to multiple drug resistance, virulence, and gene expression of M. avium.
Evaluation of a direct blood culture disk diffusion antimicrobial susceptibility test
Authors: Doern G V , Scott D R , Rashad A L , Kim K S
Published: June 2012

A total of 556 unique blood culture isolates of nonfastidious aerobic and facultatively anaerobic bacteria were examined by direct and standardized disk susceptibility test methods (4,234 antibiotic-organism comparisons). When discrepancies which could be accounted for by the variability inherent in disk diffusion susceptibility tests were excluded, the direct method demonstrated 96.8% overall agreement with the standardized method. A total of 1.6% minor, 1.5% major, and 0.1% very major discrepancies were noted.
Photochemical Destruction of the Virucidal Activities of Retinoids and Unsaturated Fatty Acids
Authors: Sands Jeffrey A.
Published: June 2012

Photochemical damage either to retinoids by near-ultraviolet radiation or to unsaturated fatty acids by near-ultraviolet radiation in the presence of a hydrophobic photosensitizer destroys the virucidal activities of the compounds, as determined by studies on the enveloped bacteriophage ø6.
Agar dilution susceptibility of Bacteroides spp. to sulfamethoxazole and trimethoprim: correlation with a disk diffusion technique
Authors: Riley T V
Published: June 2012

The minimum inhibitory concentrations of sulfamethoxazole and trimethoprim against 105 strains of Bacteroides spp. were determined by an agar dilution method, using Diagnostic Sensitivity Test agar supplemented with lysed blood. A total of 92% of the strains were susceptible to sulfamethoxazole alone (minimum inhibitory concentration, less than or equal to 50 microgram/ml), whereas only 28% were susceptible to trimethoprim alone (minimum inhibitory concentration, less than or equal to 1 microgram/ml). Susceptibility was also determined by a disk diffusion technique. For sulfamethoxazole, there was good correlation between inhibition zone diameters and minimum inhibitory concentrations. Hence, the disk diffusion test for susceptibility of Bacteroides spp. to sulfamethoxazole is suitable for routine laboratory testing. However, for trimethoprim there was a lack of correlation between the agar diffusion method and the minimum inhibitory concentrations. Three different methods for detecting synergy between sulfamethoxazole and trimethoprim against Bacteroides spp. were evaluated. With a checkerboard method, synergy was demonstrated in 96% of the strains which could be evaluated. However, this technique is unsuitable for routine testing. Two other techniques, which have been successfully used for detecting synergy with aerobic bacteria, were found to be unsatisfactory for Bacteroides spp.
In vitro antimicrobial activity evaluation of cefodizime (HR221), a new semisynthetic cephalosporin
Authors: Jones R N , Barry A L , Thornsberry C , Wilson H W
Published: June 2012

Cefodizime (HR221) is a new alpha-methoxyimino cephalosporin developed by Hoechst-Roussel with a reported serum half-life of over 2 h. In vitro susceptibility studies showed that the cefodizime spectrum includes all those Enterobacteriaceae, staphylococci, Streptococcus spp., Haemophilus spp., and Neisseria spp. normally susceptible to cefotaxime (HR756) or ceftizoxime (FK749) or both. Cefodizime was less active (two- to eightfold) than cefotaxime or ceftizoxime against some enteric species, but was the most potent drug against some strains of Morganella spp. and Proteus vulgaris. Enterococci, methicillin-resistant Staphylococcus aureus, and most Pseudomonas spp. were resistant to cefodizime (median minimum inhibitory concentrations, greater than or equal to 64 microgram/ml). Acinetobacter spp. and Pseudomonas aeruginosa strains required cefodizime concentrations of 32 microgram/ml to inhibit 50% of tested strains. Cefodizime was very stable to hydrolysis by Richmond-Sykes type I, II, III, and IV beta-lactamases, as well as the enzyme derived from Bacillus cereus. The reference PADAC and nitrocefin substrate hydrolysis by a type I beta-lactamase was markedly inhibited (greater than 80%) by cefodizime at concentrations 0.4 to 4% of substrate concentration. Cefodizime was active against 43% of bacteria which were resistant to cephalothin and cefamandole and against 58% of those resistant to aminoglycosides.
Virus inhibition assay for measurement of acyclovir levels in human plasma and urine
Authors: Moore D F , Taylor S C , Bryson Y J
Published: June 2012

A simple microplate virus inhibition assay which measures the levels of acyclovir in plasma and urine samples from patients was developed. The assay is based upon the inhibition of the cytopathic effect of herpes simplex virus type 1 on human fibroblast cells. The extent of inhibition of virus cytopathic effect, caused by dilutions of samples from patients, allowed determination of acyclovir concentrations to be made. The assay, which measured biological activity, could detect acyclovir levels of greater than or equal to 1.0 microM. Peak and valley levels measured in plasma samples from two patients were comparable to values obtained by radioimmunoassay. The assay is simple, rapid, and quantitative, and it can be adapted to routine use for a large number of specimens.
Comparative evaluation of three methods for measuring gentamicin and tobramycin in serum
Authors: Ngui-Yen J H , Hofmann T , Wigmore M , Smith J A
Published: June 2012

Three procedures (radioimmunoassay, fluorescence immunoassay, and enzyme immunoassay) for the determination of gentamicin and tobramycin levels were compared. These systems were evaluated on the basis of accuracy, reproducibility, specificity, and cost. All three systems showed a high degree of accuracy and precision. The fluorescence immunoassay gave significantly lower values for gentamicin and tobramycin at levels below 5 microgram/ml. Of the three systems, the radioimmunoassay was the least expensive, provided that a minimum of 10 analyses were performed daily; single tests required more technical time and were more costly. Costs of single tests by fluorescence immunoassay and enzyme immunoassay systems were similar. The enzyme immunoassay system performed equally well for both gentamicin and tobramycin in giving rapid and accurate results.
Activity of Di-β-Lysyl-Capreomycin IIA and Palmitoyl Tuberactinamine N Against Drug-Resistant Mutants with Altered Ribosomes
Authors: Yamada Takeshi , Teshima Tadashi , Shiba Tetsuo
Published: June 2012

The effects of 61 synthetic tuberactinomycin derivatives on polypeptide synthesis were tested in bacterial cell-free systems. Di-β-lys-capreomycin IIA was more effective than the natural product. Palmitoyl tuberactinamine N inhibited the growth of tuberactinomycin-resistant mutants and was not a ribosome inhibitor.
Comparative in vitro activity of N-formimidoyl thienamycin against gram-positive and gram-negative aerobic and anaerobic species and its beta-lactamase stability
Authors: Neu H C , Labthavikul P
Published: June 2012

The in vitro activity of N-formimidoyl thienamycin was determined against 800 gram-positive and gram-negative aerobic and anaerobic bacteria and compared with the activity of cefoxitin, cefazolin, cefamandole, cefotaxime, moxalactam, ampicillin, cefoperazone, and gentamicin. N-Formimidoyl thienamycin inhibited the majority of organisms at concentrations below 1 microgram/ml. It inhibited methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus faecalis. It inhibited beta-lactamase-producing Haemophilus influenzae and Neisseria gonorrhoeae. Unlike other new beta-lactams, it inhibited Listeria. Escherichia coli, Klebsiella pneumoniae, enterobacters, Serratia, indole-positive Proteus, Acinetobacter, Pseudomonas aeruginosa, and Bacteroides resistant to other agents were inhibited. There was minimal effect of inoculum size and aerobic versus anaerobic conditions, and serum had no effect on activity. Most minimal bactericidal concentrations were two- or fourfold greater than the minimal inhibitory concentration. N-Formimidoyl thienamycin showed partial synergy with aminoglycosides against S. aureus, S. faecalis, and many Pseudomonas and Enterobacteriaceae. It was not hydrolyzed by plasmid-mediated and chromosomal beta-lactamases.
Performance characteristics of bioassay, radioenzymatic assay, homogeneous enzyme immunoassay, and high-performance liquid chromatographic determination of serum gentamicin
Authors: Delaney C J , Opheim K E , Smith A L , Plorde J J
Published: June 2012

We compared the accuracy, precision, and between-method error of the microbiological assay, the radioenzymatic assay, the homogeneous enzyme immunoassay, and the high-performance liquid chromatographic assay for the quantitation of gentamicin in serum. Precision and accuracy were evaluated by reference samples prepared to contain 0.0 to 32.7 micrograms of gentamicin per ml. Correlations between the methods utilized patient sera with gentamicin concentrations ranging from 0.6 to 13.3 micrograms/ml. All methods were reliable within acceptable limits for routine clinical use; intermethod correlation coefficients exceeded 0.96. Relative to the microbiological assay, the alternative methods offer the advantage of rapid analysis. The elapsed times for acquiring data on a set of 10 specimens under routine operating conditions were 0.5 h by the enzyme immunoassay, 4 h by the radioenzymatic assay, 5 h by the high-performance liquid chromatographic assay, and 10 h by the microbiological assay.
Rapid, radiolabeled macrophage culture method for detection of dapsone-resistant Mycobacterium leprae
Authors: Nath I , Prasad H K , Sathish M , Sreevatsa  , Desikan K V , Seshadri P S , Iyer C G
Published: June 2012

Mycobacterium leprae cells extracted from the skin biopsies of 14 bacilliferous lepromatous patients were maintained in human-murine macrophage cultures for 3 weeks in the presence of [3H]thymidine and DDS (4,4'-diaminodiphenyl sulfone). All cultures except one containing freshly extracted viable bacilli showed significant incorporation of [3H]thymidine as compared to control cultures containing heat-killed bacilli of the corresponding strain. Six susceptible strains of M. leprae obtained from untreated, freshly diagnosed patients showed significant inhibition of the uptake of the radiolabel in the presence of 3 and 10 ng of DDS per ml per culture. Eight strains of M. leprae obtained from patients clinically suspected of DDS resistance were tested in a similar manner. These strains were also concurrently inoculated in the footpads of mice given orally 10(-2), 10(-3), and 10(-4) g of DDS per 100 g of body weight for 9 months. Concordant results were obtained by both methods: five strains were found to be resistant, one was susceptible, and one was partially resistant. Strain VIII did not incorporate [3H]thymidine in the macrophage cultures and proved to be resistant in the mouse footpad. The macrophage culture system provides a sensitive, rapid screening method for the early diagnosis of DDS resistance.
Effect of probenecid on the pharmacokinetics of moxalactam
Authors: DeSante K A , Israel K S , Brier G L , Wolny J D , Hatcher B L
Published: June 2012

The effects of probenecid on the pharmacokinetics of moxalactam were studied in normal volunteers administered a 2-min l-g intravenous infusion. The results showed that probenecid did not alter the plasma or urinary concentrations of moxalactam, its apparent volume of distribution, plasma elimination half-life, elimination rate constant, or plasma and renal clearances. Therefore, moxalactam appears to be eliminated primarily by the kidney via glomerular filtration.
Antiviral treatment of chronic hepatitis B virus infection: pharmacokinetics and side effects of interferon and adenine arabinoside alone and in combination
Authors: Sacks S L , Scullard G H , Pollard R B , Gregory P B , Robinson W S , Merigan T C
Published: June 2012

In an uncontrolled trial, 29 patients with chronic hepatitis B virus infection were treated with 93 courses of adenine arabinoside at doses ranging from 2.5 to 15 mg/kg per day. Most patients were treated concomitantly with human leukocyte interferon. Significant, but transient, neurotoxicity was seen with adenine arabinoside therapy in 44% of all courses. Manifestations of toxicity were mainly neurological and ranged from pain syndromes to tremors and, rarely, seizures. Suppression of numbers of lymphocytes was also noted. All effects were reversible with time. The extent of toxicity was dependent upon the dosage of adenine arabinoside. Treatment with interferon appeared to potentiate the occurrence of toxicity with adenine arabinoside. Arabinofuranosylhypoxanthine serum levels increased in a dose-dependent manner and tended to accumulate in interferon-treated hepatitis patients during a course of therapy. Elevated blood levels and drug accumulation were associated with toxicity in a significant fashion. Human leukocyte interferon was administered to 38 patients in 113 separate courses. Interferon side effects were rapidly reversible upon cessation of therapy. These included initial fever, myalgias, and hair loss as well as suppression of granulocytes, platelets, and lymphocytes in the blood.