bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and biological activity of tripeptidyl polyoxins as antifungal agents
Authors: Naider F , Shenbagamurthi P , Steinfeld A S , Smith H A , Boney C , Becker J M
Published: June 2012

Three tripeptidyl polyoxins were synthesized and found to inhibit Candida albicans. Compared with the naturally occurring polyoxin D, the three synthetic polyoxins had little effect on chitin synthetase when assayed with a C. albicans membrane preparation. However, all the compounds inhibited growth, affected cell morphology in a manner similar to that of polyoxin D, and were hydrolyzed by cell extracts of C. albicans. Hydrolysis did not occur extracellularly, and at least one of the synthetic polyoxins, leucyl-norleucyl-uracil polyoxin C, inhibited peptide uptake, suggesting entrance into the cell via the peptide transport system. Thus, the intact tripeptidyl polyoxins are inactive prodrugs that are converted to active moieties by cellular enzymes.
Imipenem versus moxalactam in the treatment of serious infections
Authors: Eron L J , Hixon D L , Park C H , Goldenberg R I , Poretz D M
Published: June 2012

Imipenem (formerly imipemide, N-formimidoyl thienamycin, or MK0787) was compared to moxalactam in a randomized therapeutic trial involving 39 evaluable patients with serious bacterial infections. Of those treated with imipenem, 89% were cured or improved versus 60% for moxalactam (P = 0.06). Although mucocutaneous fungal infections occurred in both groups (25 and 10%, respectively), Streptococcus faecalis superinfection was seen in two patients in the moxalactam group only. Adverse drug reactions occurred with both drugs, although bleeding occurred in three patients treated with moxalactam.
Inhibition of respiration of Escherichia coli by thioglycerol
Authors: Javor G T
Published: June 2012

Anaerobic growth on glucose significantly protected Escherichia coli from growth inhibition by thioglycerol. Methionine and anaerobiosis completely overcame growth inhibition by 2 to 90 mM thioglycerol. The respiration of aerobically growing cells was partially inhibited by 20 to 90 mM thioglycerol.
Oral antiviral drugs in experimental herpes simplex keratitis
Authors: Kaufman H E , Varnell E D , Centifanto-Fitzgerald Y M , De Clercq E , Kissling G E
Published: June 2012

Chronic oral administration of acyclovir or bromovinyl deoxyuridine to rabbits did not prevent recurrence of virus shedding or clinical corneal disease, nor did it alter the clinical course of recurrences of ocular herpetic disease or result in the appearance of resistant virus in tears.
In vitro susceptibilities of five Leptospira strains to 16 antimicrobial agents
Authors: Oie S , Hironaga K , Koshiro A , Konishi H , Yoshii Z
Published: June 2012

The in vitro activities of 16 antibiotics against five serovar strains of the genus Leptospira were determined. Five of the antibiotics (ampicillin, cefmetazole, moxalactam, ceftizoxime, and cefotaxime) exhibited a lower minimal inhibitory concentration than did penicillin G. In tests for minimal bactericidal concentration, ceftizoxime and cefotaxime were found to be more effective than penicillin G, streptomycin, tetracycline, ampicillin, and cefmetazole.
Properties of novel beta-lactamase produced by Bacteroides fragilis
Authors: Yotsuji A , Minami S , Inoue M , Mitsuhashi S
Published: June 2012

Bacteroides fragilis strains were isolated from clinical specimens. B. fragilis G-237 was highly resistant to beta-lactam antibiotics due to beta-lactamase production. The purified enzyme from this strain gave a single protein band on polyacrylamide gel electrophoresis. The isoelectric point was 4.8, and the molecular weight was estimated to be 26,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme activity was inhibited by p-chloromercuribenzoate and iodine but not by clavulanic acid or sulbactam. The purified enzyme showed a unique substrate profile by hydrolyzing at a high rate most of the cephalosporins, including cephamycin derivatives, penicillins, and imipenem (formerly imipemide, N-formimidoyl thienamycin, or MK 0787).
Characterization of tetracycline resistance plasmids from Campylobacter jejuni and Campylobacter coli
Authors: Taylor D E , Garner R S , Allan B J
Published: June 2012

Tetracycline resistance in strains of Campylobacter jejuni and Campylobacter coli was mediated by plasmids. Intra- and interspecies transfer was demonstrated within the genus Campylobacter. Buoyant densities of plasmid DNAs ranged from 1.691 to 1.694 g/cm3 (31 to 33% guanine plus cytosine). Restriction enzymes AccI, BclI, BglII, and PstI were found to be most useful for comparing the plasmids. The molecular weight of C. jejuni plasmid pMAK175 was 44.7 kilobases (29 X 10(6), and the other plasmids had similar sizes. Two plasmids from Belgian isolates of C. coli of human origin had very similar restriction enzyme profiles and are probably identical. Plasmids from human isolates of C. jejuni originating in Canada and the animal isolate of C. coli showed greater diversity. DNA homology among the campylobacter plasmids was assessed by probing the digests with a nick-translated campylobacter plasmid, pMAK175. All restriction fragments showed significant homology with pMAK175 probe DNA. No homology was noted between campylobacter plasmid DNA and plasmids specifying the four classes of tetracycline resistance determinants found in Enterobacteriaceae.
Cefoxitin inactivation by Bacteroides fragilis
Authors: Cuchural G J , Tally F P , Jacobus N V , Marsh P K , Mayhew J W
Published: June 2012

We have surveyed the susceptibility of 1,575 clinical isolates of the Bacteroides fragilis group of organisms to cefoxitin and eight other antimicrobial agents. Eleven isolates, 0.7% of the total, were highly cefoxitin resistant and had minimum inhibitory concentrations of greater than or equal to 64 micrograms/ml. These isolates were also resistant to other beta-lactam antibiotics. Of 11 isolates, 4 were able to inactivate cefoxitin in broth cultures, as measured by microbiological and high-pressure liquid chromatography assays. Two distinct patterns of cefoxitin breakdown products were detected by high-pressure liquid chromatography analysis. The beta-lactamase inhibitors clavulanic acid and sulbactam failed to show synergism with cefoxitin. These data demonstrate that members of the B. fragilis group have acquired a novel resistance mechanism enabling them to inactivate cefoxitin.
Establishment of a murine cell line resistant to arabinosyladenine and devoid of adenosine deaminase activity
Authors: Shipman C , Tong S L , Smith S H , Katlama N B , Drach J C
Published: June 2012

A population of cells stably resistant to a concentration of arabinosyladenine 100-fold greater than that tolerated by wild-type cells was selected over a period of 15 months. The cells are not cross resistant to arabinosylcytosine and may have at least one kinase with altered substrate specificity.
Influence of food on the pharmacokinetics of ketoconazole
Authors: Daneshmend T K , Warnock D W , Ene M D , Johnson E M , Potten M R , Richardson M D , Williamson P J
Published: June 2012

Eight healthy adults were given single oral doses of ketoconazole (200, 400, 600, and 800 mg) in the fasting state and with a standard breakfast at weekly intervals according to a balanced block design. Concentrations in serum were measured up to 32 h after the dose. Food did not reduce ketoconazole absorption or significantly alter peak ketoconazole concentrations in serum, though there was a food-related delay in achieving peak concentrations. At the 400- and 600-mg doses, food appeared to enhance absorption, but this effect was not seen at the 800-mg dose. With an increase in dose, the half-life and area under the serum concentration-time curve increased disproportionately, suggesting that the pharmacokinetics of ketoconazole may be dose dependent. Up to the 800-mg dose, the elimination of ketoconazole did not appear to be saturable. Administration of the drug with food is unlikely to be a cause of therapeutic failure.
Placental transfer of cefotiam dihydrochloride
Authors: Miyakawa I , Inoue H , Kuroki T , Lee H C , Azegami M , Mori N
Published: June 2012

The concentrations of cefotiam dihydrochloride (CTM) in maternal and fetal blood and in amniotic fluid were determined by bioassay in 38 women at parturition. With an intravenous infusion of 1 g of CTM, the decline in concentration of CTM in maternal blood was biphasic; CTM was not detectable at 6 h after administration. Peak levels of CTM in umbilical cord blood (13.0 to 23.9 micrograms/ml) were attained between 15 and 28 min after intravenous infusion; those in amniotic fluid (19.6 to 23.5 micrograms/ml) were attained at ca. 2.5 h.
Pharmacokinetics and therapeutic efficacy of imipenem, ceftazidime, and ceftriaxone in experimental meningitis due to an ampicillin- and chloramphenicol-resistant strain of Haemophilus influenzae type b
Authors: Sakata Y , McCracken G H , Thomas M L , Olsen K D
Published: June 2012

The pharmacokinetics and therapeutic efficacy of imipenem, ceftazidime, and ceftriaxone were compared with those of ampicillin and chloramphenicol in rabbits with experimental meningitis due to an ampicillin- and chloramphenicol-resistant strain of Haemophilus influenzae type b. The mean bacterial colony counts in cerebrospinal fluid were reduced by 49% (-1.85 log10 CFU/ml), 92% (-3.37 log10 CFU/ml), and 92% (-4.30 log10 CFU/ml) after a single dose of imipenem, ceftazidime, and ceftriaxone, respectively. The median peak cerebrospinal fluid bactericidal titers against this multiply resistant strain of H. influenzae were 1:4 for thienamycin, 1:16 for ceftazidime, and 1:256 for ceftriaxone. By contrast, no bactericidal activity was observed in cerebrospinal fluid and the mean concentrations of H. influenzae were either unchanged or slightly increased in animals treated with ampicillin or chloramphenicol.
Cefsulodin sodium therapy in cystic fibrosis patients
Authors: Cabezudo I , Thompson R L , Selden R F , Guenthner S H , Wenzel R P
Published: June 2012

Cefsulodin sodium is a narrow-spectrum cephalosporin with marked in vitro activity against clinical isolates of Pseudomonas aeruginosa. We have studied the antibiotic in a clinical trial in 10 patients admitted to the Pediatric Ward of the University of Virginia Medical Center with cystic fibrosis and recurrent acute lower respiratory tract infections with P. aeruginosa isolated from their sputa. The patients received 500 to 1,500 mg of cefsulodin every 6 hours by intravenous infusion for 10 to 22 days. Mean peak drug levels in plasma after 500, 1,000, and 1,500 mg were 46, 71, and 90 micrograms/ml, respectively, and the mean minimal inhibitory concentration of all organisms was 7.5 micrograms/ml. Detectable levels of cefsulodin in sputa were found in approximately half of the random samples and ranged from 2 to 5 micrograms/ml. The clinical response was satisfactory in nine (90%) of the patients. One patient gained weight and had improved pulmonary function tests but showed no reduction in sputum production and no improvement in arterial blood gas values. In pulmonary function tests, four of five patients tested showed an average 43% increase in forced vital capacity after initiation of therapy and five of five had an average 51% increase in forced expired volume in 1 s. No adverse effects were observed.
Comparison of ceftriaxone and traditional therapy of bacterial meningitis
Authors: Congeni B L
Published: June 2012

Forty-five children (aged 1 day to 15 years) with bacterial meningitis were randomized to receive either traditional therapy (ampicillin and chloramphenicol or gentamicin, pending sensitivity) or ceftriaxone (100 mg/kg per day in two doses for a minimum of 10 days). The etiological agents involved were similar for the two groups and included Haemophilus influenzae type b, Neisseria meningitidis, Streptococcus pneumoniae, and group B streptococcus. Repeat spinal taps were carried out 24 to 48 h after admission. Organisms were seen on the Gram stain of one patient treated with ceftriaxone, but five patients in the traditional therapy group had organisms present on Gram stain of uncentrifuged spinal fluid or positive cultures of the spinal fluid (or both). Ceftriaxone entered the cerebrospinal fluid well, and the average cerebrospinal fluid bactericidal activity for ceftriaxone 1 h after a dose was at least 60 times greater than for ampicillin or chloramphenicol. In those patients who received treatment for a long enough period of time to permit evaluation, there was one death in each group, both due to S. pneumoniae. The length of fever and complications were similar for the patients in both groups. Ceftriaxone was well tolerated; diarrhea, seen in 5 of the 22 patients who received the drug, was the most commonly encountered adverse effect. It was mild, and in no case was it necessary to discontinue the drug. Ceftriaxone appears in this preliminary study to be a safe and acceptable single agent for the treatment of bacterial meningitis in children.
High-pressure liquid chromatographic method for determination of Sch 28191 in biological fluids
Authors: Kim H , Lin C
Published: June 2012

A high-pressure liquid chromatographic method has been developed for the measurement of N-D-ornithyl amphotericin B methyl ester (Sch 28191) in biological fluid. The method involves protein precipitation with methanol, followed by separation of the supernatant on a reverse-phase column and quantitation by absorbance at 405 nm. This technique resulted in a recovery of 97%. There was a good linear relationship between the peak height ratio and Sch 28191 concentrations ranging from 0.015 to 20 micrograms/ml. In addition, this method was specific for Sch 28191 since all of its analogs tested did not interfere with the assay. The method was reproducible with a lower limit of quantitation of 0.015 microgram/ml. Serum levels obtained from this method were in good agreement with those obtained from a microbiological assay only when drug concentrations were higher than 1.5 microgram/ml. The high-pressure liquid chromatographic method is useful in monitoring serum and urine drug levels in animals and should prove to be useful for pharmacokinetic studies of the drug with therapeutic doses in humans.
Effect of protein binding on simulated intravascular and extravascular kinetics of cefotaxime in an in vitro model
Authors: Peterson L R , Van Etta L L , Fasching C E , Gerding D N
Published: June 2012

The simulated intravascular and extravascular kinetics of cefotaxime were studied in an in vitro model to evaluate the effect of antibiotic protein binding in the "intravascular" and "extravascular" space. Intravascular fluid consisted of either phosphate-buffered saline, which has no cefotaxime binding, or 3% bovine albumin, which has 63% cefotaxime binding. Extravascular spaces were filled with phosphate-buffered saline, 1.5% bovine albumin (46.6% cefotaxime binding), or 3% bovine albumin. Cefotaxime (80 mg per dose) was infused every 3 h for eight doses, and intravascular and extravascular drug concentrations were measured after doses one and eight. The corresponding intravascular and extravascular spaces were at (phosphate-buffered saline) or approaching (3% bovine albumin) equilibrium by dose eight. There were marked differences in drug concentrations achieved in the various extravascular spaces, but all could be explained on the basis of differing amounts of albumin present and the resultant differences in cefotaxime binding.
In vitro susceptibility of Nocardia asteroides to 25 antimicrobial agents
Authors: Dewsnup D H , Wright D N
Published: June 2012

Fifty-two clinical isolates of Nocardia asteroides were tested by agar dilution for their susceptibility to 25 antimicrobial agents. In general, susceptibility could not be predicted based on the antibiotic class tested. However, the beta-lactams, including third-generation cephalosporins, were generally ineffective (MIC for 90% of the organisms [MIC90], between 64 and greater than 256 micrograms/ml), whereas minocycline and doxycycline were generally effective (MIC90, 4 and 8 micrograms/ml, respectively). Cycloserine was not effective below 60 micrograms/ml. The MIC50 and MIC90 of sulfamethoxazole was 16 and 32 micrograms/ml, respectively, and that of trimethoprim varied widely (16 and greater than 256 micrograms/ml, respectively). Based on MIC90 data, only doxycycline, minocycline, sulfamethoxazole, and imipenem could be applied empirically.
Stimulation of granulocyte functions in vitro by imipenem and the renal enzyme inhibitor MK 0791
Authors: Gnarpe H , Belsheim J , Blomqvist C , Lundbäck A
Published: June 2012

Imipenem and the renal enzyme inhibitor MK 0791 (dehydropeptidase-I) were tested separately and in a 1:1 combination to delineate their effects on granulocyte functioning. Each component, as well as the combination product, was found to increase granulocyte adherence and chemotaxis at therapeutic concentrations. Phagocytosis and chemiluminescence were not found to be significantly altered by any of the drug combinations.
Antiviral activity of SK&F 21681 against herpes simplex virus
Authors: Katz E , Margalith E
Published: June 2012

SK&F 21681 (3,10-dimethyl-10-H-s-triazolo[4',3':2,3]-as-triazino-[ 5,6-b]indole) is an inhibitor of the growth of herpes simplex viruses types 1 and 2 at a concentration of 60 micrograms/ml. It inhibits the synthesis of the viral DNA and the formation of virus particles, although the viral polypeptide synthesis is not significantly affected by this compound. Mutants of herpes simplex viruses types 1 and 2 which are able to grow in the presence of SK&F 21681 were isolated. They induced normal levels of thymidine kinase and DNA polymerase activities in the infected cells and did not show resistance to either 9-[2-hydroxyethoxymethyl] guanine or phosphonoacetic acid.
Detection and quantitation of chloramphenicol by competitive enzyme-linked immunoassay
Authors: Campbell G S , Mageau R P , Schwab B , Johnston R W
Published: June 2012

A competitive enzyme-linked immunoassay for the detection and quantitation of chloramphenicol has been developed. The binding of specific rabbit antibody to solid-phase-bound chloramphenicol was competitively inhibited by free chloramphenicol in the sample to be assayed. Antibody not displaced was indicated by using a commercially available, enzyme-linked, anti-rabbit immunoglobulin preparation and reacted with added substrate. Enzyme activity, measured spectrophotometrically, was inversely proportional to the concentration of chloramphenicol in the sample. Quantitation of the antibiotic was linear to 100 ng/ml, with a lower limit of detection of 1 ng/ml (P less than 0.05). Specificity was demonstrated by the lack of inhibition by any of 31 selected antimicrobial agents or chemicals tested in the assay. Chloramphenicol sodium succinate and thiamphenicol, an experimental antibiotic similar in structure to chloramphenicol, were the only drugs found to produce cross-reactions. In addition to excellent sensitivity and specificity, the assay was shown to have good precision and economy and could be completed in approximately 24h.
Side chain modifications in lankacidin group antibiotics
Authors: McFarland J W , Pirie D K , Retsema J A , English A R
Published: June 2012

Novel N-acyl analogs of lankacidin may be prepared from 3-isocyanatolankone diformate [7,13-bis(formyloxy)-2-isocyanato-1,4,10,19-tetramethyl-16- oxabicyclo[13.2.2.]nonadeca-3,5,9,11-tetraen-17,18-dione]. Of seven such analogs evaluated in vitro only homolankacidin diformate showed significant activity. However, in a cell-free system two of the inactive analogs inhibited polypeptide synthesis as well as did lankacidin itself or erythromycin. Antibacterial activity, therefore, is a function of the ability of a congener to penetrate the bacterial cell membrane in addition to its intrinsic activity. Similarly, lankacidinol is as potent as lankacidin or erythromycin as an inhibitor of bacterial polypeptide synthesis in a cell-free system. This intrinsic activity is expressed as potent antibacterial activity against growing gram-positive cultures in O(2')-acyl derivatives with the proper lipophilicity.
Detection of PSE-2 beta-lactamase in enterobacteria
Authors: Livermore D M , Maskell J P , Williams J D
Published: June 2012

PSE-2, a plasmid-mediated beta-lactamase which was previously considered pseudomonas specific, was observed in clinical isolates of Escherichia coli, Klebsiella pneumoniae, Providencia stuartii, and Enterobacter cloacae. All four isolates transferred PSE-2 production, together with resistance to gentamicin, tobramycin, kanamycin, and sulfamethoxazole, into Escherichia coli J62-1 and Pseudomonas aeruginosa PU21. Transfer correlated with acquisition by the transconjugants of a 65-megadalton plasmid, and this element was considered to encode PSE-2 expression. The PSE-2 enzyme conferred high-level carbenicillin resistance on both J62-1 and PU21 transconjugants, although the PSE-2-producing Providencia stuartii isolate was susceptible to carbenicillin.
Capacity of a cis-diammineplatinum[II]-polyglutamic acid complex to cure Trypanosoma congolense infections in mice
Authors: Meshnick S R , Brown D , Smith G
Published: June 2012

A cis-diammineplatinum(II)-polyglutamic acid complex proved to have marked trypanocidal activity in vivo. When 5 mg of platinum per kg was administered daily for 5 days or when 20 mg of platinum per kg was administered on days 1, 3, and 6, five of five treated Trypanosoma congolense-infected mice were cured. In contrast, cis-platin was ineffective at all doses tested. We believe that the complex has a much higher therapeutic ratio than does uncomplexed drug because it is less toxic.
Growth phase in relation to ketoconazole and miconazole susceptibilities of Candida albicans
Authors: Beggs W H
Published: June 2012

The antifungal imidazoles miconazole and ketoconazole inhibit synthesis of essential cell membrane components. Furthermore, miconazole can exert direct physicochemical cell membrane damage at relatively high levels, but ketoconazole cannot. Experiments were designed to explain our previous observation that concentrations of miconazole capable of causing direct membrane damage were no more active against Candida albicans than equimolar levels of ketoconazole. When stationary-phase cells were inoculated into medium containing either drug at 3.8 X 10(-5) M, fungistatic effects were indistinguishable. If, however, such cultures were incubated 3 h before drug addition, differences were remarkable. After 3 h, miconazole caused a 99% reduction in CFU per milliliter within 20 min, but ketoconazole again was only fungistatic. The immediate onset, rapidity, and magnitude of the miconazole effect were indicative of direct lethal cell damage. Miconazole concentrations as low as 1.0 X 10(-5) M were similarly active. It was concluded that C. albicans undergoes phenotypic changes during the growth cycle that coincidentally confer susceptibility or resistance to the lethal direct membrane damage effect of miconazole. The fungistatic or metabolic effects of ketoconazole or low-level miconazole appeared to be independent of growth phase.
Purification and properties of an inducible cephalosporinase from Pseudomonas maltophilia GN12873
Authors: Saino Y , Inoue M , Mitsuhashi S
Published: June 2012

An inducible cephalosporinase was purified from Pseudomonas maltophilia GN12873. The pI was 8.4, and the molecular weight was ca. 56,000 by gel filtration or 27,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting that this enzyme had two subunits. The optimal pH and optimal temperature were 7.5 and 45 degrees C, respectively. Enzyme activity was inhibited by clavulanic acid, sulbactam, cephamycin derivatives, carbapenem antibiotics, iodine, HgCl2, and p-chloromercuribenzoate. The enzyme showed a broad substrate profile, hydrolyzing cephaloridine, cefazolin, cefsulodin, penicillin G, ceftizoxime, and ampicillin at a high rate.
Anti-Candida activity of polyoxin: example of peptide transport in yeasts
Authors: Mehta R J , Kingsbury W D , Valenta J , Actor P
Published: June 2012

The polyoxins, nucleoside peptide antibiotics, are effective inhibitors of chitin synthesis in some fungi and yeasts. Although isolated chitin synthetases appear to be equally sensitive to inhibition by polyoxins, intact yeast cells are relatively insensitive. It has been suggested that polyoxins enter cells by a peptide carrier transport mechanism. In this paper, we report results which demonstrate that changes in the growth conditions significantly affect the degree of sensitivity of Canidida albicans to the polyoxins. For example, a minimal inhibitory concentration of 0.1 micrograms/ml was obtained in a defined medium compared with a minimal inhibitory concentration of 1,000 micrograms/ml with conventional media. Various noninhibitory di- and tripeptides, when added to the media, were found to antagonize the anti-Candida activity of polyoxins. In addition, polyoxin-resistant mutants of C. albicans were shown to exhibit cross-resistance with other dipeptide antibiotics. The data reported herein support peptide transport of polyoxins in C. albicans.
Efficacy of aztreonam in treatment of experimental syphilis in rabbits
Authors: Lukehart S A , Baker-Zander S A , Holmes K K
Published: June 2012

The efficacy of aztreonam (SQ 26,776) in the therapy of active syphilis infection was evaluated in the rabbit model. Aztreonam was effective in treating active syphilis at a dose of 25 mg/kg given intramuscularly twice daily for 10 days; doses of 2.5 and 0.25 mg/kg were not effective.
In vitro susceptibilities of human and wild-type isolates of Basidiobolus and Conidiobolus species
Authors: Yangco B G , Okafor J I , TeStrake D
Published: June 2012

The in vitro activities of amphotericin B, miconazole, ketoconazole, 5-fluorocytosine, and potassium iodide (KI) were studied on human and wild-type isolates of Basidiobolus and Conidiobolus species. Of the antifungal agents tested, the imidazole derivatives, especially ketoconazole, were the most active against the agents of entomophthoromycosis. Transmission electron microscopy showed severe morphological alteration of Basidiobolus sp. exposed to 0.78 micrograms of ketoconazole per ml. The MIC and minimal fungicidal concentration of ketoconazole was often lowered in the presence of 10% fetal calf serum or antibiotic medium no. 3. Half of the Basidiobolus isolates and all Conidiobolus isolates were inhibited by amphotericin B at 0.39 micrograms/ml. None of the strains tested were inhibited or killed at maximum concentrations of 5-fluorocytosine and KI. The in vitro resistance of these fungi to KI at high concentrations suggests that the reported favorable treatment with KI may not be due to its direct effect on these fungi but rather to other, undefined factors in combination with KI. These data suggest that ketoconazole may be of use in the treatment of entomophthoromycosis, particularly in cases which are not responsive to KI.
Rosoxacin in the therapy of uncomplicated gonorrhea
Authors: Romanowski B , Austin T W , Pattison F L , Lawee D , Portnoy D , Givan K F , Li E L , Nguyen K B
Published: June 2012

In this randomized, multicentered study, 157 males and 130 females with laboratory-confirmed, uncomplicated anogenital Neisseria gonorrhoeae infections were evaluated to determine the efficacy and safety of a single 300-mg oral dose of rosoxacin versus 3.5 g of ampicillin plus 1 g of probenecid. A total of 130 males and 101 females were evaluated. Rosoxacin cured 90.3% (P = 0.053) and 94.1% (P = 0.62), respectively, whereas ampicillin was effective in 98.5 and 98% of males and females, respectively. All 39 patients with anorectal infections were cured. One penicillinase-producing N. gonorrhoeae strain was isolated and was eradicated with rosoxacin. Of 212 pretreatment isolates tested, 201 were inhibited by 0.06 micrograms or less of rosoxacin per ml. The MICs of rosoxacin for the remaining 11 isolates ranged up to 0.5 micrograms/ml. The incidence of adverse effects was relatively high (29% for the rosoxacin group versus 18% for the ampicillin group), but none of the reactions required medical intervention nor did they result in serious sequelae.
Comparative in vitro activity of ciprofloxacin against Campylobacter spp. and other bacterial enteric pathogens
Authors: Goodman L J , Fliegelman R M , Trenholme G M , Kaplan R L
Published: June 2012

A comparison was made of the in vitro activity of ciprofloxacin (Bay o 9867) with nine other antibiotics against isolates of Campylobacter jejuni, Salmonella spp., Shigella spp., Yersinia enterocolitica, Clostridium difficile, Vibrio spp., and Escherichia coli. Minimum inhibitory concentrations of ciprofloxacin were the lowest of any compound tested for all organisms except C. difficile.
Identification of small DNA fragments synthesized in herpes simplex virus-infected cells in the presence of acyclovir
Authors: McGuirt P V , Shaw J E , Elion G B , Furman P A
Published: June 2012

The effect of acyclovir on DNA synthesized in cells infected with herpes simplex virus type 1 was examined. DNA that was synthesized in infected cells in the presence of acyclovir during a short pulse with [3H]thymidine remained near the top of an alkaline sucrose gradient after centrifugation. The sedimentation characteristics of labeled DNA were not changed after chasing in isotope-free medium. The slowly sedimenting DNA was identified as viral in origin by hybridization to purified herpes simplex virus nucleocapsid DNA. When cells were infected with acyclovir-resistant virus containing mutations in the polymerase gene, the viral DNA synthesized in the presence of acyclovir was chased into high-molecular-weight DNA. These findings are consistent with chain termination of herpes simplex virus DNA in virus-infected cells.
Cefmenoxime therapy of serious bacterial infections
Authors: Gombert M E , Glasser L A , Eng R H
Published: June 2012

The efficacy and safety of cefmenoxime was evaluated in 50 patients with serious bacterial infections. These included 26 pneumonias, 18 urinary tract infections, 2 soft tissue infections, 2 bacteremias, 1 renal abscess, and 1 peritonitis. A satisfactory clinical response was seen in 47 patients (94%). Eosinophilia and thrombocytosis were seen in several patients but were generally mild and transient.
Synergistic antiviral effects of antiherpes compounds and human leukocyte interferon on varicella-zoster virus in vitro
Authors: Baba M , Ito M , Shigeta S , De Clercq E
Published: June 2012

The four antiherpes compounds acyclovir, adenine arabinoside, bromovinyldeoxyuridine, and phosphonoformic acid showed an additive to synergistic effect with human leukocyte interferon in inhibiting focus formation by three different strains of varicella-zoster virus in human embryonic fibroblasts.
Infection caused by vancomycin-resistant Streptococcus sanguis II
Authors: Shlaes D M , Marino J , Jacobs M R
Published: June 2012

A patient with bacteremia caused by vancomycin-resistant Streptococcus sanguis II is presented. This rare occurrence suggests that vancomycin may not be a completely reliable antibiotic in the treatment of infections due to viridans species of the genus Streptococcus. Gram-positive isolates from blood and otherwise sterile body fluids should be tested for susceptibility to vancomycin.
Enhanced efficacy of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine in combination with beta-interferon against herpes simplex virus type 2 in mice
Authors: Fraser-Smith E B , Eppstein D A , Marsh Y V , Matthews T R
Published: June 2012

The acyclic nucleoside 9-(1,3-dihydroxy-2- propoxymethyl )guanine (DHPG) and natural mouse interferon beta ( MuIFN -beta) were evaluated for their efficacy alone and in combination against herpes simplex virus type 2 systemic infections in mice. Intraperitoneally infected animals were treated once a day with the drugs at various concentrations for 5 days starting 24 h after inoculation. DHPG was injected subcutaneously at doses of 0.7 to 6 mg/kg. MuIFN -beta was given intraperitoneally at doses ranging from 3 X 10(3) to 3 X 10(4) IU per mouse. For DHPG alone, the effective dose at which 50% of the mice survived (ED50) was greater than 6 mg/kg. However, when given in combination with an ineffective dose of MuIFN -beta (10(4) IU per mouse), the ED50 for DHPG was 0.8 mg/kg. In addition, at the highest dose tested, MuIFN -beta alone had no protective activity against herpes simplex virus type 2 (ED50, greater than 3 X 10(4) IU per mouse). However, when given in combination with a marginally effective dose of DHPG (2 mg/kg), the ED50 for MuIFN -beta was less than 3 X 10(3) IU per mouse. Calculation of the fractional protective dose index (less than 0.23 where values of less than or equal to 0.5 are considered synergistic) indicates an enhanced protective interaction by the combination of the two drugs. These results represent the first time that potentiation of the antiviral activity of an acyclic nucleoside by interferon has been demonstrated in animal studies.
Antileishmanial activity of chlorpromazine
Authors: Pearson R D , Manian A A , Hall D , Harcus J L , Hewlett E L
Published: June 2012

The antiprotozoal activity of chlorpromazine against the pathogenic protozoan Leishmania donovani, in both its amastigote and promastigote stages, was characterized. Chlorpromazine at concentrations greater than or equal to 3.12 micrograms/ml (9.8 X 10(-6) M) produced a significant reduction in viable promastigotes. The minimal protozoacidal concentration for promastigotes, defined as that concentration which produced greater than or equal to 90% reduction in viable parasites after 18 h, was 13.8 micrograms/ml. The results were similar when promastigote viability was assessed by flagellar motility or by the ability of drug-exposed or control promastigotes to incorporate [3H]uridine and [3H]leucine. Exposure of promastigotes to 50 micrograms of chlorpromazine per ml reduced O2 consumption by 87% within 30 min and immobilized 97% of parasites. Morphological disruption of promastigotes was observed by electron microscopy. The mean minimal protozoacidal concentration of chlorpromazine for amastigotes was 13.2 micrograms/ml. Chlorpromazine given orally (20 mg/kg per day for 14 days) reduced the parasite burden in L. donovani-infected hamsters by 64.2% (P less than 0.01) as measured by the number of amastigotes in touch preparations of livers and by 67.9% (P = 0.03) as measured by the number of promastigotes derived from homogenates of spleens. This dose is ca. 10-fold greater than that tolerated by patients being treated for psychiatric illness. Although chlorpromazine will probably not be useful in the treatment of human visceral leishmaniasis, the data suggest that less-toxic phenothiazines might prove to be effective.
Pharmacokinetics of sultamicillin in mice, rats, and dogs
Authors: English A R , Girard D , Haskell S L
Published: June 2012

The irreversible beta-lactamase inhibitor sulbactam has been combined chemically via ester linkages with ampicillin to form sultamicillin . Upon oral absorption, sultamicillin is completely hydrolyzed to equimolar proportions of sulbactam and ampicillin, thereby acting as an efficient mutual prodrug. In rats, sultamicillin delivered 2 to 2.5 times greater total bioavailability for ampicillin and sulbactam than when each was used individually. Actual plasma or serum concentrations (measured in micrograms per milliliter) of ampicillin and sulbactam produced by sultamicillin were generally equivalent in rats, mice, and beagle dogs. Further studies also indicated that the components of sultamicillin were widely distributed in the various tissues of rats. These findings suggest that sultamicillin might be an effective agent against a variety of infections produced by both beta-lactamase-resistant and beta-lactamase-susceptible microorganisms.
Size and stability of a naturally occurring virus inhibitor
Authors: Coppenhaver D H , Baron J L , McKerlie M L , Sabados J , Baron S
Published: June 2012

We recently described a virus inhibitor (contact-blocking virus inhibitor) which was produced spontaneously by untransformed human and murine cells in tissue culture (S. Baron and L. McKerlie , Infect. Immun . 32:449-453, 1981). This contact-blocking virus inhibitor was characterized by broad antiviral activity, high potency, and reversible inhibition of viral attachment. Unlike interferon, the antiviral activity of the contact-blocking virus inhibitor is not species specific. An inhibitor with similar properties can also be demonstrated in many body fluids and surface secretions. We report here studies on the stability of the antiviral species which indicate that it is resistant to denaturation by heat (100 degrees C), acid (pH 2), and alkali (pH 12). The antiviral activity against all viruses tested resides in a low-molecular-weight molecule. The range of characteristics so far determined for the contact-blocking virus inhibitor distinguishes it from other virus inhibitors reported in the literature.
In vitro antibacterial activity of the combination of clindamycin and ceftazidime
Authors: George W L
Published: June 2012

A total of 49 anaerobic and 52 aerobic or facultative bacteria were tested for their susceptibilities to clindamycin and ceftazidime alone and in combination. Synergy was noted for 11 strains, whereas antagonism was not detected. The combination of clindamycin and ceftazidime may prove to be useful for the treatment of severe mixed infections caused by anaerobes and aerobes or facultative bacteria.
Cross-resistance between methicillin and cephalosporins for staphylococci: a general assumption not true for cefamandole
Authors: Frongillo R F , Bianchi P , Moretti A , Pasticci M B , Ripa S , Pauluzzi S
Published: June 2012

The antibacterial activity of cefamandole was evaluated against 120 methicillin-susceptible and methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococcal strains, using both large (10(8) CFU per ml) and small (10(4) CFU per ml) inocula. Cefamandole appeared superior to cephalothin against methicillin-resistant strains, displaying at 10 micrograms/ml a bacteriostatic and for some strains a bactericidal action against a large inoculum of bacteria.
Antibiotic susceptibility patterns in Rochalimaea quintana, the agent of trench fever
Authors: Myers W F , Grossman D M , Wisseman C L
Published: June 2012

Rochalimaea quintana, the etiological agent of trench fever, was tested by an agar dilution method for its susceptibility to the following 14 antibiotics: penicillin G, methicillin, ampicillin, cephalothin, vancomycin, doxycycline, tetracycline, erythromycin, chloramphenicol, streptomycin, kanamycin, rifampin, colistin, and amphotericin B. The MIC of each of these antibiotics was determined. The results showed that R. quintana is susceptible in vitro to these antibiotics, with the exception of vancomycin, kanamycin, streptomycin, colistin, and amphotericin B.
Pulmonary deposition and clearance of aerosolized interferon
Authors: Wyde P R , Wilson S Z , Kramer M J , Sun C S , Knight V
Published: June 2012

Small particle aerosols of a hybrid DNA recombinant human alpha interferon, A/D bgl, and a related DNA recombinant leukocyte interferon, A, were generated and delivered to mice for 23.5 h a day for 4 consecutive days. The antiviral activity of these interferons in delivery reservoirs, in the aerosols generated, and in the lungs of test mice was monitored during and after aerosol administration in cytopathic effect inhibition assays, using vesicular stomatitis virus as the indicator virus. In addition, the activity of these interferons in primary mouse embryo cells against influenza A/HK/68 (H3N2) virus was determined. The results obtained indicated that the interferon particles generated in the continuous aerosol therapy system used in these studies remained biologically active and could be readily detected in both aerosol mists and lungs of test mice; levels of exogenous interferon in the lungs equalled or exceeded levels of interferons produced endogenously during experimentally induced influenza virus infection. Titers of the exogenously administered interferons decreased gradually and disappeared from the lungs between 24 and 48 h after cessation of aerosolization. Recombinant human alpha interferon A/D, but not recombinant leukocyte alpha interferon A, significantly inhibited replication of A/HK/68 virus in primary mouse embryo cells in the in vitro studies.
Activity of ceftizoxime combined with gentamicin against 100 clinical isolates of Pseudomonas aeruginosa
Authors: King J W , Penn R L
Published: June 2012

The effects of ceftizoxime and gentamicin alone and in combination were determined against 100 Pseudomonas aeruginosa strains. Concentrations of 32 micrograms of ceftizoxime and 8 micrograms of gentamicin per ml inhibited 22 and 43% of the strains, respectively. At concentrations of ceftizoxime and gentamicin that are readily achievable in serum, 15 strains were affected synergistically and 17 strains were affected antagonistically. Gentamicin accounted for most of the anti-P. aeruginosa activity of ceftizoxime-gentamicin combinations.
Cross-resistance among cinoxacin, ciprofloxacin, DJ-6783, enoxacin, nalidixic acid, norfloxacin, and oxolinic acid after in vitro selection of resistant populations
Authors: Barry A L , Jones R N
Published: June 2012

Six different gram-negative bacilli were serially transferred through subinhibitory concentrations of seven quinolone derivatives or related organic acids. A gradual, stepwise decrease in susceptibility was noted with all seven drugs, and the resistant cultures demonstrated a concomitant cross-resistance to the other drugs.
Comparative efficacy of cefotiam versus cephalothin in the therapy of skin and soft tissue infections
Authors: Lentino J R , Stachowski M , Strikas R , Parrillo P
Published: June 2012

Cefotiam was evaluated by a comparative open-label randomized trial with cephalothin in the therapy of skin and soft tissue infections in 39 patients. The most common organism isolated was Staphylococcus aureus (78%). We established evidence of primary infection with gram-negative bacilli in four patients, three of whom were diabetic. Eight patients had mixed infections or superinfections. No patient was evaluated as a treatment failure; for 10 of 39 patients we were unable to recover an etiological agent but demonstrated a clinical cure. Cefotiam was found to be as effective as cephalothin in the therapy of skin and soft tissue infections.
Bioactivity of imipenem as a function of medium, time, and temperature
Authors: Baron E J , Hindler J A
Published: June 2012

The bioactivity of imipenem at 20 micrograms/ml in various agar and broth media which are commonly used in susceptibility test assays was measured at different storage temperatures over time. Imipenem was found to be more stable at 4 degrees C than at -20 degrees C and least stable in all media at 35 degrees C.
Identification of aminoglycoside-acetylating enzymes by high-pressure liquid chromatographic determination of their reaction products
Authors: Lovering A M , White L O , Reeves D S
Published: June 2012

A method to identify the aminoglycoside-acetyltransferase (AAC) enzymes AAC(3), AAC(2') and AAC(6') by high-pressure liquid chromatographic characterization of their products of reaction with tobramycin or sisomicin is described. Conditions are given for the chromatography of kanamycin A, netilmicin, neomycin, and apramycin, and their products of reaction, if any, with the three AAC enzymes are listed.
Recovery of norfloxacin in feces after administration of a single oral dose to human volunteers
Authors: Cofsky R D , duBouchet L , Landesman S H
Published: June 2012

Twelve healthy volunteers received single 400-mg oral doses of norfloxacin. During the ensuing 48 h, from 8.3 to 53.3% (mean, 28%) of this dose was recovered in the feces. Peak drug concentrations in fecal specimens ranged from 207 to 2,716 micrograms/g.
Characterization of trimethoprim resistance by use of probes specific for transposon Tn7
Authors: Pulkkinen L , Huovinen P , Vuorio E , Toivanen P
Published: June 2012

Transposon Tn7 codes for resistance to trimethoprim and streptomycin. For detection of Tn7 by DNA-DNA hybridization, two recombinant plasmids were constructed. The former contained a 1-kilobase BamHI fragment and the latter contained a 4.3-kilobase EcoRI-BamHI fragment of Tn7. These DNA fragments, which did not include the drug resistance genes, were used as probes for detecting Tn7-like sequences in bacterial strains by colony hybridization. They hybridized strongly to bacterial DNA known to carry Tn7 but not to DNA known to carry transposons other than Tn7. These probes were used to study the occurrence of Tn7 in bacterial strains isolated in the Turku City Hospital in Finland. Transposon Tn7 was present in 47.2% of 199 trimethoprim-resistant enterobacteria (MIC greater than or equal to 8 micrograms/ml). Among the 69 Proteus mirabilis strains studied, 75% contained Tn7, although none of these strains transferred trimethoprim resistance in conjugation tests. The reliability of colony hybridization was further confirmed by Southern hybridization to detect the Tn7-specific 2.6-kilobase HindIII restriction fragment. Colony hybridization proved to be a sensitive and rapid method for detecting Tn7-determined sequences.
Distribution of [14C]aztreonam in rat tissue
Authors: Singhvi S M , Ita C E , Shaw J M , Migdalof B H
Published: June 2012

[14C]aztreonam was administered intramuscularly (50 mg/kg) to male and female rats. Groups of 10 rats (five male and five female) were sacrificed at 0.25, 2, 6, and 24 h after dosing. Blood and various tissues were removed from six rats (three male and three female) in each group for determination of total radioactivity and unchanged aztreonam by liquid scintillation counting and thin-layer radiochromatography. The remaining rats were prepared for whole-body autoradiography. Radioactivity was distributed rapidly to most tissues and was rapidly eliminated from blood into urine and bile. Concentrations of total radioactivity in kidney, liver, small and large intestines and their contents, and urinary bladder were higher than those in serum at all the times examined. Concentrations of unchanged aztreonam in serum, kidney, liver, and lung declined at about the same rate as did that of total radioactivity in the same tissues. The results of whole-body autoradiography essentially confirmed the results of the distribution of [14C]aztreonam as determined by liquid scintillation counting. No major differences between males and females were observed when concentrations in organs common to both were compared.
Distribution of aztreonam into fetuses and milk of rats
Authors: Singhvi S M , Ita C E , Shaw J M , Keim G R , Migdalof B H
Published: June 2012

Subcutaneous administration of [14C]aztreonam (150 mg/kg) to pregnant rats was followed by the appearance of radioactive moieties in fetuses and amniotic fluid. Concentrations of both total radioactivity and unchanged aztreonam in maternal serum declined more rapidly than those in fetuses and amniotic fluid. [14C]aztreonam (150 mg/kg) was also administered subcutaneously to lactating rats. Radioactivity and unchanged aztreonam were found in the suckling pups and in the serum and milk of the dam. Results obtained by whole-body autoradiography were generally consistent with these obtained by measuring radioactivity present in the excised tissues. Autoradiographs of the pups showed detectable amounts of radioactivity in the brain; since no radioactivity was detectable in the brain of the dam, it appears that the blood-brain barrier was not fully developed in 7-day-old pups.