bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibacterial action of gramicidin S and tyrocidines in relation to active transport, in vitro transcription, and spore outgrowth
Authors: Danders W , Marahiel M A , Krause M , Kosui N , Kato T , Izumiya N , Kleinkauf H
Published: June 2012

The cyclopeptide antibiotic gramicidin S or tyrocidine in concentrations of 2 to 4 mumol/mg of membrane protein inhibited the active transport of [3H]alanine and [3H]uridine in membrane vesicles isolated from Bacillus brevis and Bacillus subtilis. We used one analog of gramicidin S and two of tyrocidine A to study the relationship between peptide structure and antibacterial action as seen in inhibiting active transport and in vitro transcription and in delaying spore outgrowth. The data showed that [Ser2,2']-gramicidin S, in which the two ornithine residues were replaced by two serines, was at least 50 times less active antibacterially and gave a low response in transport inhibition and delay of spore outgrowth compared with the natural peptide. The antibacterial activity of [Val6]-tyrocidine A was twice lower than that of tyrocidine A, and it also showed a considerable reduction in transport and transcription inhibition. [Orn7]-tyrocidine A containing two ornithine residues in positions corresponding to those in gramicidin S was almost inactive in all functions tested. The correlation between peptide structure and activity is discussed.
Activity of Ketoconazole and Its Deacyl Derivative Against
Plasmodium falciparum
and
Candida
Isolates
Authors: Pfaller Michael A. , Segal Joseph J. , Krogstad Donald J.
Published: June 2012

Deacylketoconazole was 15- to 50-fold more active against
Plasmodium falciparum
than was ketoconazole, based on [
3
H]hypoxanthine uptake and quantitative parasite counts. In contrast, there were no significant differences between these drugs in their activity against clinical isolates of
Candida
spp.
Chemical alterations in cell envelopes of polymyxin-resistant mutants of Pseudomonas aeruginosa grown in the absence or presence of polymyxin
Authors: Gilleland H E , Conrad R S
Published: June 2012

The polymyxin-resistant mutant strains H181 and H185 of Pseudomonas aeruginosa, after growth in the absence or presence of polymyxin, were compared with the polymyxin-sensitive H103 strain as to their cell envelope protein composition (determined by slab polyacrylamide gel electrophoresis) and their lipid composition. When grown in the absence of polymyxin, the H181 and H185 strains had an increased content of the outer membrane protein H1 with a decreased content of the outer membrane proteins D2 and F. After growth in the presence of polymyxin, the content of H1, D2, and F were all decreased. Significant alterations in the lipid composition of the H181 and H185 strains were found after growth in the absence of polymyxin. These lipid alterations were enhanced upon growth in the presence of polymyxin, with both strains having a reduced content of phosphatidylethanolamine and phosphatidylglycerol and an increased content of diphosphatidylglycerol and an unidentified lipid thought to be a neutral lipid. Other workers have proposed that an increased content of H1 protein is the molecular basis for polymyxin resistance in the H181 and H185 strains. Our observations make this hypothesis appear unlikely.
Penicillin tolerance in nutritionally variant streptococci
Authors: Holloway Y , Dankert J
Published: June 2012

Eleven strains of nutritionally variant streptococci were tested for their susceptibility to penicillin by a broth dilution method. All minimal inhibitory concentrations were low. It was found that plates containing only vitamin B6 (pyridoxal HCl) and cysteine did not reveal true minimal bactericidal concentrations. When penicillinase was added to the subculture medium and a staphylococcal streak was made across the plates, all 11 strains were found to have high minimal bactericidal concentrations and were shown to be tolerant to penicillin.
Determination of apalcillin and its metabolites in human body fluids by high-pressure liquid chromatography
Authors: Borner K , Lode H , Elvers A
Published: June 2012

We describe two methods for the quantitative analysis of apalcillin and its metabolites in serum and urine by reverse-phase high-pressure liquid chromatography (HPLC), a fast isocratic method for the parent drug, and a gradient method that allows the simultaneous assay of two metabolites. Serum was deproteinized with acetonitrile, and urine was diluted with buffer solution. The detection limit was about 0.5 micrograms/ml at a detection wavelength of 254 nm and 1.5 micrograms/ml at 310 nm. Within-batch precision (coefficient of variation) varied from 10.2 to 1.1% for concentrations of 7.8 and 185.3 micrograms/ml of serum, respectively. Recovery rates of 95.1 and 97.7% were found in spiked sera. Results obtained by HPLC correlated well with those from a standard microbiological assay (agar diffusion test); the resulting bivariate regression equation for serum was y-bioassay = 2.5 micrograms/ml + 0.992 X xHPLC, and that for urine was ybioassay = 12.0 micrograms/ml + 1.009 X xHPLC. At a detection wavelength of 315 nm, no interferences were observed in 10 healthy volunteers. Healthy subjects who were given 2 g of apalcillin intravenously excreted 18% of the parent drug within 24 h in the urine. Two inactive compounds were furthermore identified in urine as the isomeric forms of the penicilloic acids. Their excretion within 24 h amounted to 6.9 and 11.2% of the dose.
Pharmacokinetics of cefuroxime in infants and children with bacterial meningitis
Authors: del Rio M de los A , Chrane D F , Shelton S , McCracken G H , Nelson J D
Published: June 2012

A total of 38 patients with bacterial meningitis received either 50 or 75 mg of cefuroxime per kg of body weight given as a 15-min intravenous infusion during the first to third days of therapy. The mean peak plasma concentrations of cefuroxime after doses of 50 and 75 mg/kg were 105 and 152 micrograms/ml, respectively. In five patients, pharmacokinetic values were determined after multiple doses of 50 mg of cefuroxime per kg every 6 h. The mean peak plasma concentrations were 120 micrograms/ml after the first dose and 130 micrograms/ml after the last dose. The concentrations at 6 h were 3.25 and 11.0 micrograms/ml after the first and last doses, respectively. The elimination half-life was approximately 1.5 h, and the apparent volume of distribution was 650 ml/kg. The plasma clearance rate was 195 to 198 ml/min per 1.73 m2. Penetration into the cerebrospinal fluid, expressed as the ratio of the cerebrospinal fluid to serum areas under the curve times 100, was 6.4% in patients given 50 mg of cefuroxime per kg and 10% in those who received 75 mg/kg. The cerebrospinal bactericidal activity in 27 patients was less than or equal to 1:8; only 2 patients had bactericidal activity of less than or equal to 1:2.
Effect of methylprednisolone on entry of ampicillin and gentamicin into cerebrospinal fluid in experimental pneumococcal and Escherichia coli meningitis
Authors: Scheld W M , Brodeur J P
Published: June 2012

The influence of methylprednisolone on the passage of ampicillin and gentamicin into and activity within cerebrospinal fluid was examined in two models of experimental meningitis. Steroid pretreatment reduced the concentrations of these drugs in purulent cerebrospinal fluid of rabbits with experimental pneumococcal and Escherichia coli meningitis (P less than 0.05). However, the resultant mean concentrations of these antibiotics in cerebrospinal fluid still exceeded the minimal bactericidal concentrations of the infecting organisms. The rate of bactericidal effect in vivo was unaffected by steroid therapy in each model. Methylprednisolone did not have deleterious effects on the course of treated experimental meningitis under these short-term (24-h) experiments.
Combined effect of acyclovir and amphotericin B on the replication of pseudorabies virus in BHK-21 cells
Authors: Malewicz B , Momsen M , Jenkin H M
Published: June 2012

Acyclovir, known as an antiherpetic agent, showed an inhibitory effect on the propagation of pseudorabies virus in BHK-21 cells. The antiviral effect of acyclovir was observed by plaque reduction, as well as by the inhibition of the virus-stimulated uptake of thymidine by BHK-21 cells. Amphotericin B potentiated the antiviral activity of acyclovir. The optimal concentrations of polyene antibiotic expressing the potentiating effect were lower than required for the induction of K+ leakage from the cells. There was no evident amphotericin B-induced stimulation of thymidine incorporation into infected BHK-21 cells. The model presented may be useful to study the potentiation phenomenon of polyene macrolide antibiotics.
Effect of ketoconazole on the fungicidal action of amphotericin B in Candida albicans
Authors: Sud I J , Feingold D S
Published: June 2012

Amphotericin B-susceptible Candida albicans became resistant to the drug after growth in the presence of ketoconazole. Chromatographic analysis of cellular sterols showed that the organisms became depleted of ergosterol in parallel with the development of amphotericin B resistance. The implications of these findings are discussed in relation to combination chemotherapy with these two important antifungal agents.
Ceftriaxone diffusion into cerebrospinal fluid of children with meningitis
Authors: Latif R , Dajani A S
Published: June 2012

We evaluated the diffusion of ceftriaxone into the cerebrospinal fluid of 27 infants and children with meningitis who were receiving conventional antimicrobic therapy. Ceftriaxone was administered as a single 75 mg/kg dose and was given early or late or both in the course of the illness. Three hours after a dose, the mean cerebrospinal fluid ceftriaxone level was 5.7 micrograms/ml in patients studied early in the course of meningitis and 2.1 micrograms/ml in patients studied later in the illness. Six hours after a dose, the mean cerebrospinal fluid ceftriaxone levels early and late in meningitis were 7.2 and 2.5 micrograms/ml, respectively. The diffusion did not correlate with the leukocyte count or the protein or glucose content of the cerebrospinal fluid. Serial, simultaneous cerebrospinal fluid and plasma ceftriaxone levels were also determined in three additional patients with ventriculo-peritoneal shunt infections and external ventriculostomy drainage. The cerebrospinal fluid ceftriaxone levels in these patients ranged from 0.7 to 8.3 micrograms/ml. Our data indicate that ceftriaxone diffuses sufficiently and consistently into the cerebrospinal fluid to warrant its assessment in the treatment of meningitis.
Therapeutic significance of penicillin tolerance in experimental streptococcal endocarditis
Authors: Brennan R O , Durack D T
Published: June 2012

Tolerance to penicillin exists among the viridans group of streptococci, but its therapeutic significance is unknown. We studied the effect of penicillin alone and in combination with streptomycin, in vivo and in vitro, on three strains of dextran-producing Streptococcus sanguis serotype II which possess widely various degrees of penicillin tolerance. In rabbits with experimental endocarditis, treatment with procaine penicillin (250 mg/kg intramuscularly twice daily for 5 days) decreased the number of viable organisms in valvular vegetations from 8.82 log10 +/- 0.98 CFU/g in untreated controls to 5.31 +/- 1.19 for a highly tolerant strain, 4.22 +/- 1.05 for a less tolerant strain, and 1.79 +/- 1.72 for a nontolerant strain (P less than or equal to 0.01 for comparison between any of the four groups). None of 36 rabbits infected with tolerant strains were cured by 5 days of treatment with penicillin, but 10 of 23 animals infected with the nontolerant strain were cured (P = 0.00002). When streptomycin was given in combination with penicillin, rabbits infected with the nontolerant strain were cured within 3 days, and rabbits infected with the tolerant strain were cured within 5 days. These findings indicate that tolerance can exert a critical influence on the response of S. sanguis to penicillin therapy in vivo and that the combination of penicillin plus streptomycin exerts a synergistic effect against tolerant as well as nontolerant organisms.
Comparative in vitro activity of cefodizime, ceftazidime, aztreonam, and other selected antimicrobial agents against Neisseria gonorrhoeae
Authors: Khan M Y , Gruninger R P , Nelson S M , Obaid S R
Published: June 2012

The in vitro activities of three new beta-lactam antimicrobial agents, cefodizime, ceftazidime, and aztreonam (formerly azthreonam), were compared with those of cefotaxime, cefuroxime, cefoxitin, and penicillin against 100 beta-lactamase-negative and 42 beta-lactamase-positive Neisseria gonorrhoeae strains. The three new antimicrobial agents showed excellent activity against N. gonorrhoeae regardless of beta-lactamase production. Cefodizime was as active as cefotaxime and more active than the other test antimicrobial agents. It inhibited all isolates at a concentration of less than or equal to 0.016 micrograms/ml.
Comparative activity of amantadine and ribavirin against influenza virus in vitro: possible clinical relevance
Authors: Browne M J , Moss M Y , Boyd M R
Published: June 2012

The activities of amantadine and ribavirin against influenza A viruses were compared against low-multiplicity (plaque inhibition) and high-multiplicity (protein synthesis inhibition) infections. Our results suggest that the predictive value of in vitro data for the clinic may be improved by consideration of tests against a high-multiplicity infection.
Effect of 7 alpha substitution of cephems on their beta-lactamase stability and affinity for penicillin-binding proteins in Morganella morganii
Authors: Ohya S , Yamazaki M , Sugawara S
Published: June 2012

Cephamycins, which have a methoxy group at the 7 alpha position of their cephalosporin nuclei, were highly stable against hydrolysis by a beta-lactamase purified from a clinical isolate of Morganella morganii, whereas their 7 alpha-H analogs were rapidly hydrolyzed by the enzyme. The high stability of the cephamycins was not due to their low affinity for the enzyme, since the cephamycins strongly inhibited the enzyme in a competitive manner. In cases in which the 7 alpha-methoxy group was substituted by OC2H5, SCH3, CN, or CH3 groups, the substituted compounds still showed high stability against enzymatic hydrolysis but significantly reduced both their affinities for the enzyme and their antibacterial activities. These 7 alpha-substituted cephalosporins, except for cephamycins, also had greatly reduced affinities for target proteins, i.e., penicillin-binding proteins, of beta-lactam antibiotics. Therefore, the 7 alpha position of cephalosporins was considered to play an important role in both beta-lactamase stability and antibacterial activity.
Delayed bactericidal activity of beta-lactam antibiotics against Listeria monocytogenes: antagonism of chloramphenicol and rifampin
Authors: Winslow D L , Damme J , Dieckman E
Published: June 2012

Penicillins are considered to be the drugs of choice for the treatment of listeric meningitis, and relapse of infection is rare when treatment is given in appropriate doses for at least 14 days. Despite this, in vitro studies by others have shown that penicillins are bacteriostatic against Listeria spp. We have shown that thienamycin, penicillin G, and ampicillin are the most active beta-lactam antibiotics against Listeria spp. Of 10 strains tested, 9 were killed by less than or equal to 8 micrograms of beta-lactam antibiotics (greater than or equal to 99.9% killing) when subcultures were performed after 48, rather than 24, h of incubation. In contrast, chloramphenicol, erythromycin, doxycycline, and rifampin were bacteriostatic after 48 h of incubation. In time-kill curves, these last drugs antagonized the bactericidal action of penicillins. In view of the inefficiency of opsonization in the cerebrospinal fluid, these antagonistic combinations should probably be avoided in documented or suspected listeric meningitis.
Susceptibility of recent clinical isolates of herpes simplex virus to 5-ethyl-2'-deoxyuridine: preferential inhibition of herpes simplex virus type 2
Authors: Teh C Z , Sacks S L
Published: June 2012

We examined the in vitro susceptibilities of three reference strains and 41 recent clinical isolates of herpes simplex virus types 1 and 2 to 5-ethyl-2'-deoxyuridine. This thymidine analog exerts a type 2-preferential but not a type 2-specific antiviral effect. Utilizing a microtiter assay with BHK-21 cells, we found that the mean (+/- standard deviation) 50% inhibitory dose for herpes simplex virus type 1 isolates was 0.58 +/- 0.30 micrograms/ml as compared with 0.33 +/- 0.20 microgram/ml for herpes simplex virus type 2 isolates. Isolates were typed according to their susceptibilities to (E)-5-(2-bromovinyl)-2'-deoxyuridine and by an indirect fluorescent-antibody technique in which monoclonal antibody combinations were used. A cytotoxicity assay in which the incorporation of [1',2'-3H]deoxyuridine was measured revealed a 50% inhibitory dose of 37.5 micrograms/ml, suggesting a favorable therapeutic index for this compound.
Susceptibility of clinical isolates of Campylobacter jejuni to sixteen antimicrobial agents
Authors: Michel J , Rogol M , Dickman D
Published: June 2012

The activities of 16 antimicrobial agents against 103 clinical isolates of Campylobacter jejuni were tested. All the strains were susceptible to kanamycin and gentamicin. Chloramphenicol, nalidixic acid, and clindamycin were active against most of the strains. More than one-third of the strains were resistant to the tetracyclines and 12.5% were resistant to erythromycin.
High-pressure liquid chromatographic analysis of aztreonam in sera and urine
Authors: Pilkiewicz F G , Remsburg B J , Fisher S M , Sykes R B
Published: June 2012

Aztreonam (SQ 26,776) is a new synthetic monocyclic beta-lactam antibiotic which is specifically active against aerobic gram-negative bacteria. High-pressure liquid chromatographic (HPLC) systems were developed for the quantitative analysis of aztreonam in human, monkey, rat, mouse, and rabbit sera and urine. The HPLC conditions employed for these analyses were a muBondapak C18 column, a mobile phase made up of 0.005 M tetrabutylammonium hydrogen sulfate at pH 3.0 and acetonitrile or methanol, UV detection at 293 nm, and a flow rate of 2.0 ml/min. For human sera and urine, the mobile phase was 80% 0.005 M tetrabutylammonium hydrogen sulfate-0.005M (NH4)2SO4 and 20% acetonitrile (vol/vol). For the range of sera and urine, HPLC analyses were shown to have excellent detector linearity of aztreonam over a concentration range of 1.0 mg/ml to 0.5 microgram/ml. Correlation coefficients for plots of aztreonam peak area versus its concentration were greater than or equal to 0.990. The detection limit of aztreonam was 1.0 micrograms/ml in sera and 5.0 micrograms/ml in urine. HPLC and microbiological assays of aztreonam in human sera and urine were in good agreement.
Polyoxin D inhibits growth of zoopathogenic fungi
Authors: Becker J M , Covert N L , Shenbagamurthi P , Steinfeld A S , Naider F
Published: June 2012

We demonstrated that polyoxin D at millimolar concentrations caused marked morphological alterations of the human pathogens Candida albicans and Cryptococcus neoformans. C. albicans incubated in the presence of this drug grew in long chains that were severely swollen. Polyoxin D inhibited the growth of C. neoformans and killed cells of both the yeast and the hyphal phase of C. albicans. These observations give the first evidence that polyoxin antibiotics can kill zoopathogenic fungi.
Effect of beta-lactam antibiotics on migration and bactericidal activity of human phagocytes
Authors: Fietta A , Sacchi F , Bersani C , Grassi F , Mangiarotti P , Grassi G G
Published: June 2012

The effect of beta-lactam antibiotics upon some functions of human phagocytes was examined. Penicillins (carbenicillin and piperacillin), thienamycin, and cephalosporins (cefotetan, ceftazidime, and moxalactam) had no effect on either the random or directional migration or on the bactericidal activity of neutrophils and monocytes against Staphylococcus aureus. On the contrary, cefoperazone at therapeutic levels was shown to inhibit neutrophil chemotaxis.
Conversion of phospholipids to free fatty acids in response to acquisition of polymyxin resistance in Pseudomonas aeruginosa
Authors: Champlin F R , Gilleland H E , Conrad R S
Published: June 2012

The readily extractable lipids from a Pseudomonas aeruginosa isolate stepwise adapted to polymyxin resistance were compared with those of the susceptible parent and of a revertant strain which regained susceptibility. Significant qualitative and quantitative lipid alterations accompany the acquisition of resistance. Changes include the appearance of a major unidentified lipid (lipid X) unique to the readily extractable lipids of resistant cells. Comparative studies with parent and revertant strains indicated a significant decrease in the phospholipid content of resistant cells. Thin-layer chromatography of resistant-cell readily extractable lipids demonstrated: (i) the emergence of lipid X (36% of total readily extractable lipids), (ii) a decrease in phosphatidylethanolamine and phosphatidylglycerol, and (iii) an increase in diphosphatidylglycerol. Lipid X was purified by preparative silicic acid column chromatography and thin-layer chromatography and characterized by analytical thin-layer chromatography, column adsorption chromatography, and gas-liquid chromatography. Data from this study indicated that lipid X was a mixture of free fatty acids. The fatty acids present in lipid X were qualitatively and quantitatively the same as the fatty acids esterified to the phospholipids in the readily extractable lipids.
Therapeutic activities of 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-iodocytosine and -thymine alone and in combination with acyclovir and vidarabine in mice infected intracerebrally with herpes simplex virus
Authors: Schinazi R F , Peters J , Sokol M K , Nahmias A J
Published: June 2012

The therapeutic effectiveness of two new antiviral agents, 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-iodocytosine and 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)thymine, was compared with that of acyclovir and vidarabine. In mice inoculated intracerebrally with high 50% lethal doses of herpes simplex virus type 2, nontoxic intraperitoneal or oral treatments with the two new fluorinated antiviral agents were highly effective in reducing mortality. The two drugs were also effective when treatment was begun as late as 48 h after virus inoculation. The relative order of potencies of the drugs when compared on a molar basis or in terms of therapeutic index was 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)thymine much greater than 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-iodocytosine greater than vidarabine approximately to acyclovir. The new pyrimidine analogs were also found to lack immunosuppressive activity in mice. The combination of 1-(2-fluoro-2-deoxy-beta-=D-arabinofuranosyl)-5-iodocytosine and vidarabine was the most effective; significantly greater reduction in mortality was achieved with this combination than with either drug alone. Thirty minutes after intraperitoneal treatment with the fluorinated analogs, the drugs (or their metabolites) were transported to the brains of virus-inoculated and normal mice at levels about one-third to two thirds those in the blood. The levels of 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)thymine in the blood or brain were consistently higher than those found with equivalent intraperitoneal doses of the 5-iodocytosine analog.
In vitro evaluation of three new macrolide antimicrobial agents, RU28965, RU29065, and RU29702, and comparisons with other orally administered drugs
Authors: Jones R N , Barry A L , Thornsberry C
Published: June 2012

Three new macrolide drugs (RU28965, RU29065, and RU29702) were compared in vitro with erythromycin and five other orally administered antimicrobial agents by using 733 recent clinical isolates. All of the investigational macrolides had a spectrum very similar to that of erythromycin, but with slightly higher (two- to fourfold) minimum inhibitory concentrations against Haemophilus influenzae, staphylococci, and streptococci including Streptococcus faecalis. RU29065 and RU29702 were more active than erythromycin against Neisseria gonorrhoeae and Neisseria meningitidis. The drugs appeared to be predominantly bacteriostatic and were ineffective against gram-negative bacilli, and their minimum inhibitory concentrations were greatly increased by high inoculum concentrations. Cross-resistance between the macrolides was nearly complete, favoring the use of a single agent for in vitro susceptibility test if in vivo therapeutic differences are not observed.
In vitro activity and beta-lactamase stability of a monobactam, SQ 26,917, compared with those of aztreonam and other agents
Authors: Neu H C , Labthavikul P
Published: June 2012

SQ 26,917 is a monobactam antibiotic. Its in vitro activity was compared with those of aztreonam, cefotaxime, ceftazidime, and moxalactam. SQ 26,917, which contains a beta-methyl configuration on the beta-lactam ring, was similar in activity to aztreonam with the exception of greater activity against Pseudomonas aeruginosa isolates. SQ 26,917 had no activity against gram-positive isolates or anaerobic bacteria. It was not hydrolyzed by common plasmid and chromosomal beta-lactamases.
Effect of inoculum size on Haemophilus influenzae type b susceptibility to new and conventional antibiotics
Authors: Laferriere C , Marks M I , Welch D F
Published: June 2012

Thirty-three Haemophilus influenzae type b isolates, including beta-lactamase acetyltransferase-positive strains, were tested by microtiter broth dilution for susceptibility to eight beta-lactam compounds and chloramphenicol. All antibiotics except ampicillin and chloramphenicol were highly bactericidal against all isolates at an inoculum of 10(5) CFU/ml. However, at an inoculum of 10(5) CFU/ml, the minimal bactericidal concentrations of all drugs except ceftriaxone were above levels usually achievable in cerebrospinal fluid. Results of time-kill studies confirmed this inoculum effect. In vivo studies are needed to test the clinical impact of these observations.
Properties of PSE-2 beta-lactamase and genetic basis for its production in Pseudomonas aeruginosa
Authors: Philippon A M , Paul G C , Jacoby G A
Published: June 2012

The properties of PSE-2 beta-lactamase have been examined by using two new PSE-2-producing plasmids, pMG33 and pMG74, as well as plasmid R151, found in Pseudomonas aeruginosa. PSE-2 beta-lactamase resembled other PSE enzymes in activity against carbenicillin, but it also resembled OXA enzymes, such as OXA-1, in rapid hydrolysis of oxacillin, cloxacillin, and methicillin and in inhibition by sodium chloride but not by cloxacillin. Antisera that inactivated TEM-1, TEM-2, OXA-1, or PSE-1 and PSE-4 beta-lactamase failed to cross-react with PSE-2, which thus appears to be immunologically distinct. The plasmids determining PSE-2 varied in geographical origin, size, transfer proficiency, and incompatibility specificity, but all determined resistance to carbenicillin, gentamicin, kanamycin, streptomycin, spectinomycin, sulfonamide, and tobramycin. From a pUZ8-R151 recombinant plasmid in Escherichia coli, the PSE-2 beta-lactamase gene could be transposed to a second plasmid in a 6.4-megadalton unit together with resistance to gentamicin, kanamycin, streptomycin, spectinomycin, sulfonamide, and tobramycin. Transposition was recA independent. We propose the designation Tn1404 for this unit, which, like transposons carrying OXA-1, PSE-1, PSE-4, and some transposons determining TEM-1, includes genes for beta-lactam, aminoglycoside, and sulfonamide resistance.
Clindamycin enhances opsonization of Staphylococcus aureus
Authors: Milatovic D , Braveny I , Verhoef J
Published: June 2012

Staphylococcus aureus 502A was grown in the presence of one-third of the minimal inhibitory concentration of clindamycin. Phagocytosis of the antibiotic-treated bacteria by human polymorphonuclear leukocytes was significantly enhanced, compared with that of the untreated control (P less than 0.001). Study of opsonization kinetics by a chemiluminescence assay demonstrated that clindamycin-treated staphylococci were opsonized more rapidly than control bacteria and that the serum concentration required for sufficient opsonization was lower. Complement was consumed much faster, and the opsonic fragment C3b was fixed more rapidly to the bacterial surface when the staphylococci were preincubated with clindamycin. Electron micrographs showed an alteration of the staphylococcal cell wall after clindamycin treatment.
In vitro activity of teichomycin compared with those of other antibiotics
Authors: Neu H C , Labthavikul P
Published: June 2012

The glycopeptide antibiotic teichomycin had in vitro activity comparable to that of vancomycin against most gram-positive species, and it inhibited methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. It was twofold more active against many S. aureus and S. epidermidis isolates than was vancomycin. Teichomycin had activity comparable to that of vancomycin against Listeria monocytogenes and Streptococcus faecalis. It was generally more active against streptococci than was vancomycin. There were no major differences between minimal inhibitory concentrations and minimal bactericidal concentrations of these drugs. Teichomycin acted synergistically with gentamicin against some bacteria.
Effect of subminimal inhibitory concentrations of antimicrobial agents on the piliation and adherence of Neisseria meningitidis
Authors: Kristiansen B E , Rustad L , Spanne O , Bjorvatn B
Published: June 2012

Neisseria meningitidis is known to be highly resistant to lincomycin (minimum inhibitory concentration greater than 32 micrograms/ml). However, during studies on meningococcal piliation, we noticed a significant reduction in the number of pili after cultivation on lincomycin-containing selective media. This observation was followed up by in vitro and in vivo studies on the relation between lincomycin and meningococcal adherence to human epithelial cells. We found a remarkable decrease in in vitro piliation and adherence after exposure to lincomycin at concentrations as low as 0.05 micrograms/ml. By giving four healthy meningococcal carriers lincomycin orally for 3 to 6 days, the possible in vivo effect of lincomycin was studied. A marked decrease in the meningococcal counts of the pharyngeal secretion was observed. One person completely lost his meningococcal strain during the observation period.
Rifampin affects polymorphonuclear leukocyte interactions with bacterial and synthetic chemotaxins but not interactions with serum-derived chemotaxins
Authors: Gray G D , Smith C W , Hollers J C , Chenoweth D E , Fiegel V D , Nelson R D
Published: June 2012

Three independent experimental approaches support the hypothesis that rifampin competes for receptors on polymorphonuclear leukocytes (PMLs) with small peptide chemoattractants, e.g., N-formylmethionylleucylphenylalanine (FMLP), but not with serum-derived chemoattractants (C5a). First, rifampin inhibited chemotaxis induced with FMLP but reversed the immobilization of PMLs that occurred at high FMLP concentrations. Second, rifampin competed with radiolabeled FMLP for binding sites on PMLs and displaced already-bound radiolabeled FMLP. Third, rifampin blocked and reversed the bipolar shape changes induced in PMLs by FMLP. These effects occurred at concentrations attained during rifampin therapy and were not due to rifampin toxicity. In contrast, no effect of rifampin was observed on serum-derived chemoattractants (C5a) in any of the three systems. The evidence suggests, therefore, that rifampin is a ligand for FMLP-type receptors on PMLs.
Effect of gentamicin treatment on adenylate cyclase and Na+, K+-ATPase activities in renal tissues of rats
Authors: Queener S F , Luft F C , Hamel F G
Published: June 2012

Gentamicin (20 mg/kg) treatment of male rats reduced Na+,K+-ATPase activity by 32% in renal cortical plasma membranes. In contrast, adenylate cyclase stimulation by isoproterenol or a guanyl nucleotide or both was enhanced by as much as twofold in glomeruli and in plasma membranes of gentamicin-treated rats. These effects of gentamicin are suggested to be related to the changes in renal phospholipid metabolism produced by the drug.
Depression of adenosylmethionine content of Escherichia coli by thioglycerol
Authors: Javor G T
Published: June 2012

The mechanism of growth inhibition of Escherichia coli by thioglycerol was probed. The extent of growth inhibition depended on the ratio of thioglycerol to initial cell concentration. Exogenously added methionine and several methionine analogues reversed the inhibition of 2 to 40 mM thioglycerol. Exposure to thioglycerol elevated the intracellular concentration of methionine, but the level of S-adenosylmethionine was depressed. Thioglycerol was methylated in vivo to 3-methylthio-1,2-propanediol.
Effect of temocillin in combination with other beta-lactam antibiotics
Authors: Verbist L , Verhaegen J
Published: June 2012

The antibacterial interactions of temocillin with other beta-lactams were tested by checkerboard combination in Mueller-Hinton agar against 146 strains of members of the family Enterobacteriaceae, 35 Pseudomonas aeruginosa strains, and 35 Staphylococcus aureus strains. Most combinations showed a moderate degree of synergism. In only one Klebsiella strain was minor antagonism observed between temocillin and ampicillin.
Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study
Authors: Eby G A , Davis D R , Halcomb W W
Published: June 2012

As a possible treatment for common colds, we tested zinc gluconate lozenges in a double-blind, placebo-controlled, clinical trial. One 23-mg zinc lozenge or matched placebo was dissolved in the mouth every 2 wakeful h after an initial double dose. After 7 days, 86% of 37 zinc-treated subjects were asymptomatic, compared with only 46% of 28 placebo-treated subjects (P = 0.0005). Side effects or complaints were usually minor and consisted mainly of objectionable taste and mouth irritation. Zinc lozenges shortened the average duration of common colds by about 7 days.
Incorporation of amino acid-derived carbon into tylactone by Streptomyces fradiae GS14
Authors: Dotzlaf J E , Metzger L S , Foglesong M A
Published: June 2012

Washed cells from 72-h cultures of Streptomyces fradiae GS14 were used to examine the distribution of radiolabel from 14C-amino acids and related compounds into tylactone, CO2, and cells. Test compounds were categorized according to products of their oxidative degradation. Those compounds known to produce propionyl-coenzyme A by direct catabolic oxidation were designated as group I. Group II included those compounds oxidized to methylmalonyl-coenzyme A via succinyl-coenzyme A and the tricarboxylic acid cycle. Group III contained compounds known to be oxidized to acetoacetyl-coenzyme A. The total amount of label recovered after 60 min ranged from 3 to 65%. Although label from all test compounds except proline (group II) and lysine (group III) was incorporated into tylactone after 60 min, label from group I and group III compounds was incorporated at levels five times greater than label from group II compounds. From 55 to 75% of the recovered label from propionate (I), asparagine (II), glutamine (II), glutamate (II), alpha-ketoglutarate (II), and succinate (II) was recovered as 14CO2. From 75 to 95% of the recovered label from the remaining compounds tested was located in the cells. Based on the data, a pathway for the role of amino acids in the biosynthesis of tylactone is proposed.
Liquid chromatographic assay of ceftizoxime in sera of normal and uremic patients
Authors: McCormick E M , Echols R M , Rosano T G
Published: June 2012

The application of high-pressure liquid chromatography assays for cephalosporin serum concentrations is difficult in uremic patients because of interference from nondialyzable substances. We developed a high-pressure liquid chromatography method for determining the serum concentration of ceftizoxime in normal and uremic patients. The method involves protein precipitation with acetonitrile, followed by removal of the acetonitrile with dichloromethane. Separation was accomplished with a reverse-phase (C-18) column and a mobile phase of 13% acetonitrile and 2.8% acetic acid. UV detection at 310 nm was used to monitor the peaks. This assay produced a linear relationship between peak height ratio and ceftizoxime concentration from 1.5 to 100 micrograms/ml. Samples from 30 patients were assayed by this method and by a bioassay, with a good correlation of results (r = 0.9832). The method was applicable equally to normal and uremic serum samples.
Prophylaxis of Candida albicans infection in neutropenic mice with liposome-encapsulated amphotericin B
Authors: Lopez-Berestein G , Hopfer R L , Mehta R , Mehta K , Hersh E M , Juliano R L
Published: June 2012

The efficacy of liposome-encapsulated amphotericin B in the prophylaxis of disseminated Candida albicans infections in neutropenic mice was studied. The administration of liposome-encapsulated amphotericin B was associated with protection against infection with C. albicans when used at doses of greater than or equal to 2 mg of amphotericin B per kg of body weight. Neither empty liposomes nor free amphotericin B showed prophylactic efficacy.
Importance of the hydrophobic sulfoxide substituent on nontoxic analogs of sparsomycin
Authors: Ash R J , Fite L D , Beight D W , Flynn G A
Published: June 2012

Nontoxic analogs of sparsomycin were competitive inhibitors of puromycin in the peptidyl transferase assay with Escherichia coli polysomes. The sensitivity of HeLa cells in vitro to the analogs was used as a preliminary index of cellular toxicity. In vitro killing of HeLa cells by this class of compounds correlated well with in vivo 50% lethal doses. The data indicate that modification of the hydrophobic sulfoxide substituent on sparsomycin decreases the toxicity of the molecule for mammalian cells by several hundredfold. Such modifications have less of an effect on the inhibitory activity of the compounds for peptidyl transferase. The differential effects of an analog active against bacterial but not mammalian cells was due to a decreased uptake of the compound by HeLa cells.
Correlation of antibiotic resistance with Vmax/Km ratio of enzymatic modification of aminoglycosides by kanamycin acetyltransferase
Authors: Radika K , Northrop D B
Published: June 2012

Kinetic data for the antibiotic-modifying enzyme kanamycin acetyltransferase AAC(6')-IV have been determined for five aminoglycoside antibiotics (amikacin, gentamicin C1a, kanamycin A, sisomicin, and tobramycin) and compared with close-interval determinations of the minimal inhibitory concentrations of the same antibiotics against Escherichia coli W677 harboring the resistance plasmid pMH67. These minimal inhibitory concentrations for the resistant bacteria varied from 80 to 800 micrograms/ml. Of the kinetic parameters Vmax, Km, and Vmax/Km ratio only Vmax/Km ratio had a linear correlation with minimal inhibitory concentrations (r = +0.818) at pH 7.8, where all antibiotics produced substrate inhibition, but not at pH 6.0, where they did not. The correlation with only Vmax/Km ratio has implications regarding the expression of resistance within the dynamics of the bacterial cell (i.e., antibiotic uptake versus modification), whereas substrate inhibition presents an opportunity to search for new chemotherapeutic agents which will combat resistance directly.
Bactericidal activities of five antibiotics during short-term exposure to coagulase-negative staphylococci
Authors: Fischer P R , Gooch W M , Walker M L , Storrs B
Published: June 2012

After a 1-h exposure to concentrations used for topical prophylaxis in neurosurgical procedures, bacitracin, vancomycin, and oxacillin were bactericidal against more than 90% of 48 body fluid isolates of coagulase-negative staphylococci. More than 10% of isolates survived despite exposure for 4 h to concentrations of gentamicin and streptomycin greater than those employed for topical prophylaxis.
In vitro activity of ciprofloxacin compared with those of other new fluorinated piperazinyl-substituted quinoline derivatives
Authors: Van Caekenberghe D L , Pattyn S R
Published: June 2012

The in vitro antimicrobial activity of ciprofloxacin (Bay o 9867) was compared with those of the other new fluorated piperazinyl-substituted quinoline derivatives: norfloxacin, ofloxacin, and pefloxacin, as well as with those of the earlier analogs, nalidixic acid and oxolinic acid. Virtually no resistance against the new fluorated piperazinyl-substituted quinoline derivatives was observed. As a rule, ciprofloxacin was about four times more active in vitro than the other new fluorated piperazinyl-substituted quinoline derivatives. The antibacterial spectrum of the new fluorated piperazinyl-substituted quinoline derivatives included, among other susceptible species, Pseudomonas aeruginosa, Streptococcus faecalis, Staphylococcus spp., and members of the family Enterobacteriaceae. In the case of ciprofloxacin, ofloxacin, and perfloxacin, anaerobes were included in the antibacterial spectrum as well. There was no cross resistance between the earlier analogs and the new fluorated piperazinyl-substituted quinoline derivatives. Regression analysis of MIC pairs for individual strains illustrated almost mathematical correlation between the antimicrobial activities of the quinoline derivatives.
Development of resistance to cephalosporins in clinical strains of Citrobacter spp
Authors: Gootz T D , Jackson D B , Sherris J C
Published: June 2012

The predominant beta-lactam antibiogram of Citrobacter freundii resembles that of Enterobacter cloacae in demonstrating resistance to cephalothin and cefoxitin with susceptibility to the newer cephalosporins. Four representative strains of C. freundii were reversibly induced to high-level beta-lactamase production by cefoxitin, and mutants with stable, high-level production were selected with cefamandole. The mutants were resistant to several second- and third-generation cephalosporins. Comparisons of isoelectric points and substrate profiles of beta-lactamases from wild-type, induced wild-type, and mutant organisms suggested a close relationship to those from E. cloacae and indicated that C. freundii mutants, like those of E. cloacae, were derepressed for production of beta-lactamase. One primary isolate of C. freundii resembled the mutants in all characteristics. In contrast, most strains of Citrobacter diversus were susceptible to all cephalosporins, and two representative strains showed neither inducible nor mutational resistance. Cefoxitin induction to enhanced beta-lactamase production was demonstrated in a cephalothin-resistant isolate, and a derepressed mutant was selected with cefotaxime. The beta-lactamase from this C. diversus strain differed substantially in substrate profile from that of E. cloacae and C. freundii.
Pharmacokinetics of vancomycin in patients undergoing continuous ambulatory peritoneal dialysis
Authors: Blevins R D , Halstenson C E , Salem N G , Matzke G R
Published: June 2012

The pharmacokinetics of vancomycin were studied in four patients on continuous ambulatory peritoneal dialysis. After a single intravenous infusion of 10 mg/kg of total body weight, multiple blood, urine, and dialysate samples were collected during a 72-h evaluation period. The steady-state volume of distribution was 0.73 +/- 0.07 (mean +/- standard deviation) liters/kg with a beta half-life of 90.2 +/- 24.2 h. The continuous ambulatory peritoneal dialysis clearance of vancomycin was 1.35 +/- 0.35 ml/min, and the serum clearance was 6.4 +/- 1.1 ml/min. Peritoneal dialysate concentrations of vancomycin were rapidly attained after the intravenous infusion and averaged 2.2 +/- 0.7 mg/liter throughout the 72-h observation period. A loading dose of 23 mg/kg followed by a maintenance dose of 17 mg/kg every 7 days should attain and maintain therapeutic serum and dialysate concentrations. More frequent dosing may be necessary for less susceptible organisms.
Pharmacokinetics of ceftazidime in normal and uremic subjects
Authors: Leroy A , Leguy F , Borsa F , Spencer G R , Fillastre J P , Humbert G
Published: June 2012

The pharmacokinetics of ceftazidime, administered as a single intravenous dose of 15 mg/kg given in a bolus injection over 3 min, were investigated in 5 normal subjects and in 19 uremic patients. The subjects studied were divided into five groups according to values for endogenous creatinine clearance (CLCR): group I, five subjects with CLCR greater than 80 ml/min; group II, five patients with CLCR = 30 to 80 ml/min; group III, six patients with CLCR = 10 to 30 ml/min; group IV, four patients with CLCR = 2 to 10 ml/min; and group V, four anuric patients on hemodialysis. A two-compartment open model was used to calculate the pharmacokinetic parameters. In normal subjects, the mean apparent elimination half-life was 1.57 +/- 0.13 h. The central distribution volume and the apparent volume of distribution were 0.127 +/- 0.023 and 0.230 +/- 0.015 liter/kg, respectively. Of the injected dose, 83.6 +/- 3.6% was eliminated in the urine as parent drug within 24 h. The terminal half-life increased with impairment of renal function to about 25 h in severely uremic patients. Impairment of function did not significantly modify the half-life at alpha phase, central distribution volume, or apparent distribution volume. A 6- to 8-h hemodialysis procedure reduced concentrations of ceftazidime in plasma by approximately 88%, and the elimination half-life was 2.8 +/- 0.2 h. There was no evidence of accumulation of ceftazidime in four patients with severe and chronic impairment of function who received doses of 0.5 to 1.0 g every 24 h for 10 days.
Effect of halothane on the replication of animal viruses
Authors: Bedows E , Davidson B A , Knight P R
Published: June 2012

Five RNA- and two DNA-containing viruses were propagated in Vero cells and tested for their ability to replicate in the presence of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane), a commonly used inhalational anesthetic. Halothane did not affect poliovirus replication at any anesthetic concentration tested, but all other viruses were either partially or totally inhibited by clinical doses of the anesthetic. Replication of Sendai virus, simian virus 40, vesicular stomatitis virus, and herpes simplex virus type 1 were moderately inhibited by halothane exposure. At concentrations of 2.2% (vol/vol) halothane, peak virus titers were reduced by ca. 2 orders of magnitude for vesicular stomatitis virus and simian virus 40, 3.5 orders of magnitude for Sendai virus, and 4 orders of magnitude for herpes simplex virus. Newcastle disease virus and measles virus were the most susceptible to exposure to halothane. Total inhibition of the replication of these viruses occurred at 1.6 to 2.0% halothane. All of the viruses whose replication was susceptible to the action of halothane were inhibited in a concentration-dependent manner. Furthermore, with the exception of simian virus 40, the inhibition of the replication of all viruses was reversible after halothane removal, although total recovery of virus synthesis was not observed unless the culture medium was changed or the pH was adjusted after anesthetic removal.
Ornithyl amphotericin methyl ester treatment of experimental candidiasis in rats
Authors: Galgiani J N , VanWyck D B
Published: June 2012

After intravenous Candida albicans infection, rats received orinthyl amphotericin methyl ester, amphotericin B, or diluent intravenously. At doses of 0.1 and 0.5 mg/kg, the drugs were equally effective in preventing deaths. However, at doses of 2.0 mg/kg, mortality after treatment with amphotericin B was greater than that after placebo, whereas orinthyl amphotericin methyl ester was fully protective.