bluuebunny/crossref_metadata_2025 huggingface dataset:
Silver-nylon: a new antimicrobial agent
Authors: Deitch E A , Marino A A , Gillespie T E , Albright J A
Published: June 2012

The potential effectiveness of a silver nylon (SN) fabric as an antimicrobial agent was evaluated in a series of in vitro experiments. The results indicated that silver ions from the SN fabric penetrated 2 mm of agar and killed a challenge of 6.9 X 10(7) Pseudomonas aeruginosa, 4.1 X 10(7) Staphylococcus aureus, and 1.4 X 10(7) Candida albicans organisms per cm2 of SN fabric after 24 h of incubation at 37 degrees C. To determine some of the microbicidal limits of the SN, the distance between the SN fabric and the microbial challenge was increased. Increasing the height of the agar column overlying the SN fabric diminished the inhibitory effect of SN on microbial growth. For each increase in agar height of 2 mm, up to a total height of 8 mm, the effectiveness of SN to inhibit microbial growth decreased by a factor of 10. This distance-related decrease in the microbicidal ability of SN could be overcome by placing the SN fabric in contact with the agar column for 24 to 72 h before microbial challenge. On the basis of these experiments, it appears that SN is an effective antimicrobial agent, although further work must be performed before it is applied clinically.
Interactions of beta-lactam antibiotics and antineoplastic agents
Authors: Ueda Y , Saito A , Fukuoka Y , Yamashiro Y , Ikeda Y , Taki H , Yasuda T , Saikawa I
Published: June 2012

The in vitro interactions of four beta-lactam antibiotics and five antineoplastic agents were examined with 100 clinically isolated strains of four species of gram-negative bacilli. Generally, by the checkerboard dilution method, beta-lactam antibiotics, when tested in combination with mitomycin C, bleomycin, or 5-fluorouracil, showed synergistic action, whereas when tested in combination with carboquone, they showed antagonistic action. Almost no combinations of adriamycin showed the interactions. Among beta-lactam antibiotics, piperacillin was more frequently synergistic than cefoperazone, cefazolin, or carbenicillin when tested in combination with each antineoplastic agent against various species.
Activity of Brodimoprim and Metioprim Alone and in Combination with Sulfonamides Against Anaerobic Bacteria
Authors: Wüst Jürg , Schwarzenbach Jannpeter
Published: June 2012

The activities of the 2,4-diamino-5-benzylpyrimidines brodimoprim and metioprim against anaerobic bacteria were tested alone and in combination with sulfonamides. Alone they were two to four times more active than trimethoprim, but in combination with sulfonamides, their activity was slightly lower than that of trimethoprim plus sulfamethoxazole.
Scarring as a factor affecting the eradication of microorganisms from the kidney in pyelonephritis
Authors: Miller T
Published: June 2012

The inability of antimicrobial agents to penetrate scarred renal tissue may explain some therapeutic failures. We examined the effect of scarring on antimicrobial therapy by using a unique animal model in which both kidneys were infected to the same degree but only one kidney was scarred. Scar formation could not explain the failure of ampicillin or nitrofurantoin to eradicate renal infection, but co-trimoxazole was less effective in the presence of tissue damage and scar formation than in their absence.
Relationship between antifungal activity and inhibition of sterol biosynthesis in miconazole, clotrimazole, and 15-azasterol
Authors: Taylor F R , Rodriguez R J , Parks L W
Published: June 2012

The availability of Saccharomyces cerevisiae mutants which are defective in sterol biosynthesis makes it possible to determine whether the ability of several antifungal agents to inhibit cell growth is due to their effect on sterol production. 15-Aza-24-methylene-8,14-cholestadien-3 beta-ol (15-azasterol) is known to block the reduction of the sterol delta 14 bond following C-14 demethylation. This agent inhibits the growth of wild-type S. cerevisiae but does not inhibit the growth of a strain that is defective in the removal of the C-14 methyl group of lanosterol and in the introduction of the 5,6 double bond. 15-Azasterol does not inhibit the growth of a sterol auxotrophic strain growing on an exogenous supply of sterol. Therefore, the effect of 15-azasterol on sterol biosynthesis is clearly the cause of its ability to inhibit growth. On the other hand, growth inhibition by two imidazole antifungal agents, clotrimazole and miconazole, cannot be ascribed to their ability to prevent the removal of the C-14 methyl group of lanosterol, because they inhibit the growth of the sterol auxotrophic strain as well as that of the demethylase mutant.
Susceptibility of the Bacteroides fragilis group in the United States in 1981
Authors: Tally F P , Cuchural G J , Jacobus N V , Gorbach S L , Aldridge K E , Cleary T J , Finegold S M , Hill G B , Iannini P B , McCloskey R V , O'Keefe J P , Pierson C L
Published: June 2012

The minimal inhibitory concentrations of nine antimicrobial agents was determined for over 750 clinical isolates of the Bacteroides fragilis group of anaerobic bacteria collected from nine centers in the United States during 1981. High resistance rates were documented for cefoperazone, cefotaxime, and tetracycline. Cefoxitin had the best activity of the beta-lactam antibiotics, whereas moxalactam and piperacillin had good activities. The resistance rate for clindamycin was 6%. There were no metronidazole- or chloramphenicol-resistant isolates encountered. There were significant differences in susceptibility among the various species of the B. fragilis group, particularly with moxalactam, cefoxitin, and clindamycin. Clustering of clindamycin-, piperacillin-, and cefoxitin-resistant isolates was observed at different hospitals. The variability of resistance rates with the beta-lactam antibiotics and clindamycin indicates that susceptibility testing of significant clinical isolates should be performed to define local resistance patterns.
Effect of growth phase on the bactericidal action of chloramphenicol against Haemophilus influenzae type b and Escherichia coli K-1
Authors: Feldman W E , Manning N S
Published: June 2012

The bactericidal action of chloramphenicol against six Haemophilus influenzae type b isolates and six Escherichia coli K-1 isolates was compared. Cells were grown in antibiotic-free medium into the late-stationary and mid-exponential phases of growth, and inocula of 10(5) to 10(6) cells per ml were added to fresh media containing 1 or 10 micrograms of chloramphenicol per ml for H. influenzae isolates, 80 micrograms of chloramphenicol per ml for E. coli isolates, or no chloramphenicol (antibiotic free). Quantitative kinetic studies indicated that each chloramphenicol concentration killed H. influenzae cells in the stationary phase of growth significantly more rapidly than it did those in the exponential phase of growth (P less than 0.001; analysis of variance). E. coli in either the stationary or the exponential phase were killed at the same rate by 80 micrograms of chloramphenicol per ml (P greater than 0.05). These results suggest that chloramphenicol may kill these organisms by different mechanisms.
Effect of several antiviral agents on human lymphocyte functions and marrow progenitor cell proliferation
Authors: Wingard J R , Hess A D , Stuart R K , Saral R , Burns W H
Published: June 2012

Toxicity to hematopoiesis and lymphocytic function are major considerations in the clinical applicability of antiviral agents. We have examined the toxicities of five antiviral agents showing activity against herpesviruses: vidarabine, acyclovir, (E)-5-(2-bromovinyl)-2'-deoxyuridine, trifluorothymidine, and (S)-9-(2,3-dihydroxypropyl)adenine. The drugs were tested in vitro for inhibition of herpes simplex virus type 1 and human cytomegalovirus replication, effects on marrow progenitor cell growth, effects on lymphocyte responses to mitogen and alloantigen stimulation, and effects on several lymphocyte cytotoxic responses. In general, lymphocyte proliferative responses were inhibited by the various drugs at lower concentrations than were cytotoxic activities. Acyclovir and (E)-5-(2-bromovinyl)-2'-deoxyuridine were the least toxic drugs tested, with antiviral indices exceeding 10,000. Vidarabine and trifluorothymidine were more toxic, with antiviral indices generally between 10 and 100. (S)-9-(2,3-dihydroxypropyl)-adenine was the most toxic, with several antiviral indices between 1 and 10.
Comparative in vitro susceptibilities of anaerobic bacteria to cefmenoxime, cefotetan, and N-formimidoyl thienamycin
Authors: Owens W E , Finegold S M
Published: June 2012

The in vitro activities of cefmenoxime, cefotetan, and N-formimidoyl thienamycin were compared with those of other antimicrobial agents (metronidazole, clindamycin, cefoxitin, and moxalactam) against anaerobic bacteria. The data obtained indicate that N-formimidoyl thienamycin exhibits excellent activity against anaerobic bacteria; cefotetan and cefmenoxime, though less active, should be of value in treating selected anaerobic infections.
Detection of endotoxin in antibiotic solutions with Limulus amoebocyte lysate
Authors: Case M J , Ryther S S , Novitsky T J
Published: June 2012

Twenty-eight antibiotics were tested with the Limulus amoebocyte lysate assay to determine their non-inhibitory concentrations (NICs). The Limulus amoebocyte lysate assay was found to be a valid test for most of the antibiotics tested; the NICs were found to be greater than the minimum valid test concentrations. Borderline results were obtained with cefamandole nafate and neomycin sulfate. Polymyxin B and colistimethate contained too much endotoxin to permit determination of NICs. The NIC of tetracycline hydrochloride was dependent on the initial concentration of antibiotic. This dependence was most likely caused by the amount of base required to adjust the pH before testing.
9-(3,4-dihydroxybutyl)guanine, a new inhibitor of herpesvirus multiplication
Authors: Larsson A , Oberg B , Alenius S , Hagberg C E , Johansson N G , Lindborg B , Stening G
Published: June 2012

A new compound, 9-(3,4-dihydroxybutyl)guanine, has been synthesized and its antiherpes activity determined. 9-(3,4-Dihydroxybutyl)guanine was selectively phosphorylated by herpes simplex virus thymidine kinase and had a high affinity for this enzyme, with an inhibition constant of 1.5 microM. In cell culture, replication of different strains of herpes simplex virus types 1 and 2 was inhibited to the extent of 50% by 4 to 18 microM (RS)-9-(3,4-dihydroxybutyl)guanine. The (R)-enantiomer of this compound was more inhibitory than the (S)-enantiomer. Herpesvirus DNA synthesis was selectively inhibited by (RS)-9-(3,4-dihydroxybutyl)guanine in infected cells, and a low cellular toxicity was observed. (RS)-9-(3,4-Dihydroxybutyl)guanine had a therapeutic effect when applied topically to guinea pigs with cutaneous herpes simplex type 1 infections and to rabbits with herpes keratitis. Oral treatment of a generalized herpes simplex type 2 infection in mice had a therapeutic effect.
Concentrations of cefoperazone in cerebrospinal fluid during bacterial meningitis
Authors: Cable D , Overturf G , Edralin G
Published: June 2012

Cefoperazone was administered to 15 patients with bacterial meningitis before lumbar punctures were performed. Patients received one of the following three dosage regimens before collection of cerebrospinal fluid (CSF): one dose of 50 mg/kg (maximum, 2 g; group I), one dose of 100 mg/kg (maximum, 4 g; group II), three doses of 100 mg/kg each every 8 h (maximum, 4 g each dose; group III). Of 44 CSF samples, 26 had detectable cefoperazone levels (59%); drug concentrations in CSF ranged from less than 0.8 to 11.5 micrograms/ml (median, 1.97 micrograms/ml). Although the percentage of patients with detectable cefoperazone levels in CSF was higher in group III (69%) than in group II (64%) or group I (50%), the differences were not statistically significant; however, the mean drug concentration in CSF in group I (1.53 micrograms/ml) was significantly lower than that in group III (3.1 micrograms/ml). A high protein concentration in CSF (as an indicator of meningeal inflammation) correlated best with high cefoperazone concentrations in CSF. These findings differ from previous investigations of cefoperazone penetration into CSF; however, cefoperazone may not penetrate reliably into CSF and therefore may not be an optimal candidate drug for the treatment of bacterial meningitis.
Biliary levels of ceforanide
Authors: Kenady D E , Ram M D
Published: June 2012

Ceforanide levels in plasma, gallbladder bile, gallbladder tissue, and common bile duct were studied in 10 patients with normal biliary tracts and in 35 patients with biliary disease at various intervals after intravenous injection of 1 g of the drug. Peak blood levels were obtained within 1 h of administration (mean, 67 +/- 15 micrograms/ml). Patients with a normal bilary tract, as well as patients with chronic cholecystitis and a patent cystic duct, achieved high gallbladder bile levels of ceforanide within 2 h (mean, 76 +/- 25 micrograms/ml) and attained even higher levels by 4 h (mean, 182 +/- 51 micrograms/ml). However, all patients with chronic cholecystitis and an occluded cystic duct had very low drug concentrations in the gallbladder bile (14 +/- 7 micrograms/ml at 2 h). Despite this difference in gallbladder bile levels, ceforanide levels of 21 +/- 3 micrograms/g were achieved at 1 to 3 h in gallbladder tissue in both groups with chronic cholecystitis. The concentration of ceforanide in common bile duct was 149 +/- 59 micrograms/ml at 2 h after administration, with levels over 60 micrograms/ml present from 1 to 4 h after administration. These results indicate that ceforanide reaches high levels in the biliary tract. Its potential value in the prevention and treatment of biliary infections should be assessed.
Susceptibility of bovid herpesvirus 1 to antiviral drugs: in vitro versus in vivo efficacy of (E)-5-(2-Bromovinyl)-2'-deoxyuridine
Authors: Babiuk L A , Acres S D , Misra V , Stockdale P H , De Clercq E
Published: June 2012

The relative efficacies of a variety of antiviral drugs against bovid herpesvirus 1 was investigated. (E)-5-(2-Bromovinyl)-2'-deoxyuridine and trifluorothymidine were found to be inhibitory at doses of 0.01 micrograms/ml in in vitro yield reduction and plaque reduction assays. In contrast, acylovir was inactive even at concentrations as high as 1,000 micrograms/ml. Other drugs, including phosphonoformic acid, 9-beta-D-arabinofuranosyladenine, 5-iodo-2-deoxyuridine, and 1-beta-D-arabinofuranosylcytosine were active at concentrations previously shown to inhibit herpes simplex virus. Oral administration of (E)-5-(2-bromovinyl)-2'-deoxyuridine to calves infected with bovid herpesvirus 1 had no effect on the level of virus shedding, clinical signs, or susceptibility to secondary bacterial infection with Pasteurella haemolytica. The reason for this lack of in vivo activity was that sufficient levels of the drug in blood were not achieved by oral administration.
Intranasal administration of gentamicin in human subjects
Authors: Rubinstein A
Published: June 2012

The effectiveness of gentamicin administered by the intranasal route in healthy human volunteers was studied. Thirty minutes after gentamicin in a solution of 1% sodium glycocholate was administered at 2 mg/kg of body weight, gentamicin concentrations of 2.48 +/- 0.42 mg/ml were present in the sera. Serum concentrations decreased to 0.94 +/- 0.13 mg/ml at 180 min. No serious side effects were observed. There was slight local irritation after a single dose. When administered intranasally without glycocholate, gentamicin was not present in the sera in detectable amounts.
Pharmacokinetics of ceftazidime in male and female volunteers
Authors: Sommers D K , Walters L , Van Wyk M , Harding S M , Paton A M , Ayrton J
Published: June 2012

The pharmacokinetic behavior of ceftazidime was assessed after single bolus intravenous injections of 1 g to 12 male and 12 female volunteers. The kinetic handling of the drug was essentially identical in the two sexes, exhibiting two-compartment model characteristics. However, the peripheral compartment volume of distribution of ceftazidime was smaller in the females (mean 3.95 liters, compared with 6.15 liters), and this was attributed to a smaller extracellular fluid volume. Eight volunteers in each group also received single 1-g doses of ceftazidime into the vastus lateralis and gluteus maximus muscles. The time to peak concentration was longer in the women, and it was longer after injection into the gluteus maximus in both sexes, presumably because of differences in local blood flow. The bioavailability of ceftazidime may have been slightly reduced by delays in absorption. Again, body and renal clearances were similar for both sexes when allowance was made for differences in distribution volume.
Modified broth-disk surveillance of clindamycin-resistant Bacteroides fragilis group
Authors: Zar F A
Published: June 2012

The modified broth-disk susceptibility test was used to assess the incidence of clindamycin resistance in the Bacteroides fragilis group. Over a 34-month period, 544 isolates were tested, 21 (4%) of which were found to be resistant. There was no significant difference in resistance among the six species, and resistance did not increase with time. In a 12-disk assay, the concentrations of clindamycin achieved approximated the concentrations expected (expected breakpoint, 4.8 micrograms/ml).
Comparison of cephalothin and ceforanide prophylaxis in cardiac surgery with cardiopulmonary bypass
Authors: Karney W , Correa-Coronas R , Zajtchuk R , Schwartz J , Smith L P , Tramont E
Published: June 2012

Eighty-five patients undergoing cardiac surgery with cardiopulmonary bypass were given either cephalothin or ceforanide perioperatively in randomized, blinded fashion. The incidence of surgically related, postoperative infections was 23% for the cephalothin- and 26% for the ceforanide-treated groups. There were no statistically significant differences that could be identified between patients who became infected and those who remained free of infections, although the time spent in the operating theater was longer for the former group. Ceforanide achieves adequate levels in plasma and myocardial tissue that are sustained several hours after a 0.5-g parenteral dose and allows a 12-h interval between doses. Other currently available agents would have to be administered more frequently to achieve similar results.
Effect of osmotic blood-brain barrier disruption on gentamicin penetration into the cerebrospinal fluid and brains of normal rabbits
Authors: Strausbaugh L J , Brinker G S
Published: June 2012

Rapid infusion of hyperosmolar solutions into the internal carotid artery transiently disrupts the blood-brain barrier, permitting entry of substances that are ordinarily excluded from the nervous system. This study compared gentamicin concentrations in the cerebrospinal fluid (CSF) and brain tissue of rabbits receiving intracarotid infusions of 2 molal mannitol with those in three groups of control animals. After catheter placement and intravenous gentamicin administration (20 mg/kg), rabbits received either 2 molal mannitol in the internal carotid artery, 2 molal mannitol intravenously, 0.9% saline in the internal carotid artery, or 0.9% saline intravenously. Mannitol and saline were administered in 8-ml bolus injections over 40 s. After 2 h, serum, CSF, and brain specimens were obtained for antibiotic assay. Gentamicin concentrations in serum were comparable in all groups (mean concentrations ranged from 14.6 to 17.9 micrograms/ml at 60 min and from 5.7 to 7.4 micrograms/ml at 135 min), but gentamicin concentrations in CSF and brains were significantly higher in animals in the group receiving mannitol in the internal carotid artery. In this group the mean gentamicin concentration in CSF, 5.3 micrograms/ml, was twofold greater than those in the other three groups (range, 1.7 to 2.6 micrograms/ml). Similarly, the mean gentamicin concentration in the brains of animals in the group receiving mannitol in the internal carotid artery, 2.3 micrograms/g was significantly higher than those in the other groups (mean of measurable values, 1.4 micrograms/g, in all three control groups). Osmotic disruption of the blood-brain barrier enhanced the penetration of gentamicin into CSF and brain tissue.
Statistical comparison of the antibacterial activities of broad-spectrum penicillins against gram-negative bacilli
Authors: Fass R J
Published: June 2012

Minimal inhibitory concentrations (MICs) or two alpha-carboxypenicillins (carbenicillin and ticarcillin) and three acylaminopenicillins (azlocillin, mezlocillin, and piperacillin) for 300 aerobic and facultative gram-negative bacilli were determined by a microdilution method and compared by parametric statistical tests. Within each group of penicillins, MICs were highly interrelated; MICs of one antibiotic were readily predictable based on knowledge of MICs of another antibiotic. Ticarcillin was consistently more active than carbenicillin by approximately one dilution step, but the relative activities of the acylaminopenicillins varied by bacterial species. The acylaminopenicillins were generally more active than the alpha-carboxypenicillins, particularly against alpha-carboxypenicillin-resistant organisms. There were exceptions, however, and antibiotic MICs in one group were not readily predictable on the basis of the knowledge of antibiotic MICs in the other group. The enhanced antibacterial potencies and spectra of the acylaminopenicillins against gram-negative bacilli make these antibiotics potentially useful therapeutic agents. It is not necessary for clinical laboratories to routinely perform susceptibility tests with all five antibiotics.
Comparison of polyacrylamide and agarose gel thin-layer isoelectric focusing for the characterization of beta-lactamases
Authors: Vecoli C , Prevost F E , Ververis J J , Medeiros A A , O'Leary G P
Published: June 2012

Plasmid-mediated beta-lactamases from strains of Escherichia coli and Pseudomonas aeruginosa were separated by isoelectric focusing on a 0.8-mm thin-layer agarose gel with a pH gradient of 3.5 to 9.5. Their banding patterns and isoelectric points were compared with those obtained with a 2.0-mm polyacrylamide gel as the support medium. The agarose method produced banding patterns and isoelectric points which corresponded to the polyacrylamide gel data for most samples. Differences were observed for HMS-1 and PSE-1 beta-lactamases. The HMS-1 sample produced two highly resolvable enzyme bands in agarose gels rather than the single faint enzyme band observed on polyacrylamide gels. The PSE-1 sample showed an isoelectric point shift of 0.2 pH unit between polyacrylamide and agarose gel (pI 5.7 and 5.5, respectively). The short focusing time, lack of toxic hazard, and ease of formulation make agarose a practical medium for the characterization of beta-lactamases.
Pharmacokinetics of metioprim in normal subjects and patients with impaired renal function
Authors: Vergin H , Bishop-Freudling G B , Kaiser W , Köhler M , Strobel K , Reutter F W
Published: June 2012

The pharmacokinetics of metioprim, a new competitive inhibitor of bacterial dihydrofolate reductases, were studied after a single oral dose of 100 mg in two young healthy subjects, four elderly volunteers, and eight patients with impaired renal function. The pharmacokinetic parameters of unchanged metioprim were derived by analyzing plasma level curves using a two-compartment model. Plasma half-lives determined for the beta phase were 10.5 to 11.5 h in young volunteers, 12.0 to 12.9 h in elderly subjects, and 13.2 to 15.3 h in patients with renal impairment. A significant correlation between the overall elimination rate constant and the creatinine clearance was demonstrated.
Rapid drug susceptibility testing of mycobacteria in tissue culture medium
Authors: Nozawa R T , Yokota T
Published: June 2012

Mycobacteria grew rapidly in FST medium (tissue culture medium F12 supplemented with 5% serum and 0.05% Tween 80). Growth of Mycobacterium tuberculosis and other niacin-negative mycobacteria in flat-bottomed, 96-well tissue culture plates was estimable by the naked eye within 3 to 5 days when mycobacteria were inoculated at 0.1 to 0.01 Klett units (5 X 10(4) to 0.5 X 10(4) CFU) per well. Spontaneous resistant variants of M. tuberculosis to isoniazid arose and grew in the medium within 2 weeks of culture. A total of 56 clinically isolated mycobacteria whose drug susceptibilities had been tested by a conventional method were tested in FST medium for minimal inhibitory concentrations of streptomycin, ethambutol, rifampin, and isoniazid. The minimal inhibitory concentrations of these drugs in FST medium strictly coincided with the drug susceptibility patterns obtained by a conventional method, except for 3 of 224 estimations.
Activities of aztreonam and new cephalosporins against infrequently isolated gram-negative bacilli
Authors: Strandberg D A , Jorgensen J H , Drutz D J
Published: June 2012

The susceptibilities of 159 clinical isolates of glucose nonfermentative gram-negative bacilli were determined for eight new monobactam or beta-lactam antibiotics. Imipemide (N-formimidoyl thienamycin) was effective against the largest number of species, although not against Pseudomonas maltophilia. Cefoperazone and ceftazidime, but not cefsulodin, were active against infrequently isolated Pseudomonas species. Aztreonam, moxalactam, cefotaxime, and ceftizoxime demonstrated selective activity against several species, including certain amino-glycoside-resistant isolates.
Broad-spectrum antiviral activity of 2-beta-D-ribofuranosylselenazole-4-carboxamide, a new antiviral agent
Authors: Kirsi J J , North J A , McKernan P A , Murray B K , Canonico P G , Huggins J W , Srivastava P C , Robins R K
Published: June 2012

The relative in vitro antiviral activities of three related nucleoside carboxamides, ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide), and selenazole (2-beta-D-ribofuranosylselenazole-4-carboxamide), were studied against selected DNA and RNA viruses. Although the activity of selenazole against different viruses varied, it was significantly more potent than ribavirin and tiazofurin against all tested representatives of the families Paramyxoviridae (parainfluenza virus type 3, mumps virus, measles virus), Reoviridae (reovirus type 3), Poxviridae (vaccinia virus), Herpes-viridae (herpes simplex virus types 1 and 2), Togaviridae (Venezuelan equine encephalomyelitis virus, yellow fever virus, Japanese encephalitis virus), Bunyaviridae (Rift Valley fever virus, sandfly fever virus [strain Sicilian], Korean hemorrhagic fever virus), Arenaviridae (Pichinde virus), Picornaviridae (coxsackieviruses B1 and B4, echovirus type 6, encephalomyocarditis virus), Adenoviridae (adenovirus type 2), and Rhabdoviridae (vesicular stomatitis virus). The antiviral activity of selenazole was also cell line dependent, being greatest in HeLa, Vero-76, and Vero E6 cells. Selenazole was relatively nontoxic for Vero, Vero-76, Vero E6, and HeLa cells at concentrations of up to 1,000 micrograms/ml. The relative plating efficiency at that concentration was over 90%. The effects of selenazole on viral replication were greatest when this agent was present at the time of viral infection. The removal of selenazole from the medium of infected cells did not reverse the antiviral effect against vaccinia virus, but there was a gradual resumption of viral replication in cells infected with parainfluenza type 3 or herpes simplex virus type 1 (strain KOS). However, the antiviral activity of ribavirin against the same viruses was reversible when the drug was removed.
Prospective randomized trial of piperacillin monotherapy versus carboxypenicillin-aminoglycoside combination regimens in the empirical treatment of serious bacterial infections
Authors: Gribble M J , Chow A W , Naiman S C , Smith J A , Bowie W R , Sacks S L , Grossman L , Buskard N , Growe G H , Plenderleith L H
Published: June 2012

Piperacillin as a single agent was compared in a prospective randomized trial with carboxypenicillin-aminoglycoside combinations in empirical therapy of serious bacterial infections. The difference in the clinical response rates with piperacillin (77% of 26 infection episodes) and combination therapy (75% of 24 infection episodes) were not statistically significant. Fewer adverse effects occurred in the piperacillin-treated group (42%) than in the combination-treated group (71%) (P = 0.0399 by Fisher's exact test), although neither nephrotoxicity nor hypokalemia alone was significantly less frequent in patients receiving piperacillin. However, the emergence of resistant organisms during therapy was more frequent among patients receiving piperacillin alone (42% of patients) than among patients receiving combination therapy (17% of patients) (P = 0.465 by Fisher's exact test). Moreover, emergence of resistance accounted for 5 of 9 patients with treatment failure, superinfection, or both when piperacillin was used as a single agent, compared with 2 of 10 similar patients in the combination group (P = 0.1299 by Fisher's exact test). The use of piperacillin as a single agent in the treatment of serious bacterial infections is not advocated, and the addition of an aminoglycoside to prevent emergence of resistance during empirical therapy of such infections is strongly recommended.
Susceptibility of Gardnerella vaginalis to cephradine
Authors: Goldstein E J , Kwok Y Y , Sutter V L
Published: June 2012

The activity of cephradine and the influence of pH on its activity against 70 Gardnerella vaginalis strains were determined. Serial dilutions of cephradine (0.062 to 256 micrograms/ml) were incorporated into Dunkelberg agar, inoculated with a Steers replicator, incubated in 5% CO2 for 48 h, and examined. The minimal inhibitory concentrations for 90% of the isolates were 16 and 8.0 micrograms/ml at pH 7.0 to 6.0 and 5.5, respectively.
Effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine on human cytomegalovirus replication in vitro
Authors: Mar E C , Cheng Y C , Huang E S
Published: June 2012

We studied the effect of a novel purine acyclic nucleoside, 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), on human cytomegalovirus (HCMV) replication. The susceptibility of HCMV to this drug was monitored in cell culture by plaque reduction assay. HCMV replication of various strains was inhibited to the extent of 50% by 1 to 5 microM DHPG. DHPG was highly specific in its anti-HCMV activity, since at concentrations as high as 100 microM it did not exert any detectable inhibitory effect on uninfected cell macromolecular synthesis and cell growth. At concentrations of 2 to 4 microM, the drug inhibited the synthesis of six virus-specific polypeptides with molecular weights of 200,000 (VP200), 150,000 (VP150), 67,000 (VP67), 54,000 (VP54), 32,000 (VP32), and 27,000 (VP27) up to 96 h after infection. HCMV DNA synthesis was also considerably suppressed at concentrations of 2 to 4 microM DHPG. Upon removal of the inhibitor, however, viral DNA synthesis resumed and infectious virus reappeared, indicating that this inhibition was a virostatic reversible-type inhibition.
Radiometric macrophage culture assay for rapid evaluation of antileprosy activity of rifampin
Authors: Mittal A , Seshadri P S , Prasad H K , Sathish M , Nath I
Published: June 2012

The antileprosy effect of rifampin was evaluated by a newly developed rapid in vitro assay wherein 31 human-derived strains and 1 armadillo-derived strain of Mycobacterium leprae were maintained for 2 and 3 weeks, respectively, in murine and human macrophages in the presence of [3H]thymidine. Of these strains, 27 showed significant incorporation of the radiolabel in cultures of live bacilli as compared with control cultures of heat-killed bacilli of the same strain. Consistent and significant inhibition of [3H]thymidine uptake was observed in M. leprae resident cultures with 3 to 200 ng of rifampin per ml as compared with similar cultures without the drug. In general, an increase in percent inhibition was seen from 3 to 20 ng/ml, with marginal increases at 40, 50, and 100 ng/ml. M. leprae strains appear to be remarkably susceptible to this drug in the in vitro assay.
High-pressure liquid chromatographic analysis of ceftazidime in serum and urine
Authors: Leeder J S , Spino M , Tesoro A M , MacLeod S M
Published: June 2012

A rapid and sensitive high-pressure liquid chromatographic procedure was developed for quantitative analysis of a new semisynthetic cephalosporin, ceftazidime, in serum and urine. A good linear relationship was established between peak height and the amount of ceftazidime injected over a concentration range of 1.9 to 30 micrograms/ml. Recovery was approximately 90% at concentrations of 3, 15, and 30 micrograms/ml. The method is specific for ceftazidime, with no interference noted from 11 other beta-lactam antibiotics tested. The assay is accurate, reproducible, and useful for pharmacokinetic studies in humans as demonstrated in two subjects.
Bacteriostatic and fungostatic action of catecholamide iron chelators
Authors: Bergeron R J , Elliott G T , Kline S J , Ramphal R , St James L
Published: June 2012

Iron starvation as a means of controlling the proliferation of microorganisms was evaluated in vitro with spermidine catecholamide iron chelators. The growth of Escherichia coli and Pseudomonas aeruginosa was sensitive only to (D,L)-parabactin, whereas the growth of Candida albicans and Staphylococcus aureus was sensitive to a variety of catecholamide chelators. The disappearance of catecholamide activity upon methylation of the catechol hydroxyls, as well as iron reversal experiments, strongly suggests that the mechanism by which these compounds suppress growth is dependent upon their ability to sequester iron.
Orally administered ketoconazole: route of delivery to the human stratum corneum
Authors: Harris R , Jones H E , Artis W M
Published: June 2012

Delivery of ketoconazole to human stratum corneum was studied. Thirteen healthy volunteers, three patients with chronic fungal disease and one patient with palmar-plantar hyperhidrosis were given 400 mg of ketoconazole daily for various lengths of time. The ketoconazole content of palmar stratum corneum, eccrine sweat, sebum, and serum was measured by high-pressure liquid chromatography (sensitivity, 0.005 to 0.010 microgram/ml). Palmar stratum corneum obtained after 7 and 14 days of daily administration contained up to 14 micrograms of ketoconazole per g. Ketoconazole was not found in sebum after 7 or 14 days of daily ingestion of the antimycotic agent. Sebum from three patients with chronic fungal infection treated for greater than 9 months contained ketoconazole (means, 4.7 micrograms/g). Thermogenic whole body eccrine sweat contained a mean of 0.059 microgram/ml on day 7 and 0.084 microgram/ml on day 14 of daily administration. Ketoconazole appeared in thermogenic whole body eccrine sweat and palmar hyperhidrotic sweat within 1 h after a single oral dose. Partition studies of ketoconazole containing eccrine sweat demonstrated a 10-fold greater concentration in the sediment phase (desquamated keratinocytes) compared with the clear supernatant phase. In vitro studies with [3H]ketoconazole-supplemented supernatant sweat revealed preferential binding to stratum corneum, hair, and nails and its partitioning to lipid-rich sebum. We conclude that eccrine sweat rapidly transports ketoconazole across the blood-skin barrier, where it may bind or partition to keratinocytes and surface lipids.
Efficacy of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine against primary and recrudescent genital herpes simplex virus type 2 infections in guinea pigs
Authors: Fraser-Smith E B , Smee D F , Matthews T R
Published: June 2012

The acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) was evaluated for its efficacy in protecting guinea pigs from primary and recrudescent infections of herpes simplex virus type 2. Vaginally infected guinea pigs were treated twice a day with DHPG at 25 mg/kg per dose for 3 weeks. Subcutaneous doses were started 3 h, 24 h, or 5 weeks after virus inoculation. Treatment starting at 3 or 24 h reduced the severity of the primary infection by greater than 70% when lesions were graded for 3 weeks; lesion duration was lessened by greater than 55%. For 6 weeks after treatment, the number of recrudescent lesions was reduced by greater than 60%, and the duration of the recrudescences declined by greater than 40%. When dosing was started at 3 h postinfection, 33% of the animals did not develop any sign of primary or recrudescent infection throughout the 9-week test. By comparison, all the animals treated with DHPG starting at 24 h or with saline became infected. A 3-week DHPG regimen starting 5 weeks postinfection reduced the number of animals that developed recrudescent lesions by 70%. When treatment ended, however, recrudescent episodes in the animals increased to the level of saline-treated controls.These results suggest that (i) DHPG is highly effective in reducing the severity of both primary and recrudescent lesions of herpes simplex virus type 2, (ii) early treatment of a primary infection or treatment of recrudescences reduces the incidence of recrudescences, and (iii) the drug appears to have no effect on the latent form of the virus, as the incidence of recrudescences increases when DHPG treatment is ended.
Comparative pharmacokinetics of apalcillin and piperacillin
Authors: Lode H , Elvers A , Koeppe P , Borner K
Published: June 2012

The pharmacokinetics of apalcillin and piperacillin, each administered intravenously as a single 2-g dose, were compared in 10 volunteers in a randomized study of crossover design using bioassay and high-pressure liquid chromatographic procedures. The concentrations of both penicillins in serum were determined over a period of 12 h and in urine over 24 h. Concentrations of apalcillin and piperacillin at the end of the 15-min infusion were similar; however, at 8 h, concentrations of piperacillin were below measurable levels, whereas concentrations of apalcillin were still measurable at 10 h. Pharmacokinetic parameters were calculated according to a two-compartment open model. The area under the curve and the half-life for apalcillin were larger than for piperacillin. On the other hand, renal clearance of piperacillin was substantially greater than that of apalcillin. Of the apalcillin excreted via the kidneys, approximately one-fifth was eliminated as two microbiologically inactive penicilloic acid derivatives. The nonrenal clearance of apalcillin was 79% of total clearance. Binding of apalcillin to serum protein was almost twice that of piperacillin.
Twice-daily intramuscular ceforanide therapy of Staphylococcus aureus endocarditis in parenteral drug abusers
Authors: Greenman R L , Arcey S M , Gutterman D A , Zweig R M
Published: June 2012

Twice-daily intramuscular ceforanide therapy of Staphylococcus aureus endocarditis in parenteral drug abusers was compared in a randomized prospective trial with intravenous cephapirin therapy. Dosage regimens were ceforanide, 1 g every 12 h, and cephapirin, 2 g every 4 h. Mean minimal inhibitory and bactericidal concentrations of ceforanide for S. aureus treated with ceforanide were 0.78 and 1.56 microgram/ml compared to cephapirin for patient isolates of 0.08 and 0.14 microgram/ml, respectively. Serum killing levels with ceforanide were 1:5.7 and 1:1.5 at peak and trough levels, compared to 1:134 (peak) and 1:4.2 (trough) with cephapirin. Despite this apparent in vitro advantage of cephapirin, patients treated with ceforanide did as well as those with cephapirin. Of 16 ceforanide-treated patients, all responded initially to therapy, and 15 were cured with 28 days of therapy. One patient relapsed at the end of therapy. Of 16 cephapirin-treated patients, 1 was a clinical and microbiological failure, and 3 other relapsed at the end of therapy. In addition, one ceforanide-treated patient and two cephapirin-treated patients developed central nervous system abscesses. These were cured with drainage and continuation of antibiotic therapy. Ceforanide was well tolerated by the intramuscular route. Cost analysis suggests that therapy with intramuscular ceforanide would result in an approximate 70% decrease in drug therapy cost when compared to intravenous cephapirin. Ceforanide appears to be a safe, efficacious, convenient, and relatively inexpensive drug for treating staphylococcal endocarditis in parenteral drug abusers.
Mechanism of action of AC-1370 on phagocyte functions
Authors: Ohnishi H , Inaba H , Mochizuki H , Kosuzume H
Published: June 2012

The mechanism of action of a new semisynthetic cephalosporin AC-1370 on phagocyte functions was investigated. AC-1370 enhanced phagocytic functions of macrophages and neutrophils. AC-1370 bound to 27.4% of mouse peritoneal resident cells. Most of the AC-1370-binding cells were macrophages, and few neutrophils bound AC-1370. Culture supernatant of mouse macrophages cultured with AC-1370 significantly augmented phagocytic functions of mouse neutrophils. This activity of the culture supernatant of AC-1370-stimulated macrophages was abolished by digestion with trypsin but not by heat treatment at 56 degrees C for 30 min. The mechanism of the activation of phagocyte functions by AC-1370 is proposed as follows. First, AC-1370 binds to macrophages and causes their activation. Second, trypsin-sensitive and heat-stable soluble factor(s) is released from these macrophages. And finally, neutrophil functions are activated by the factor(s).
Plasmid-mediated tetracycline resistance in Haemophilus ducreyi
Authors: Albritton W L , Maclean I W , Slaney L A , Ronald A R , Deneer H G
Published: June 2012

Clinical isolates of Haemophilus ducreyi were shown to be resistant to tetracycline. Resistance was associated in some strains with a 30-megadalton plasmid capable of transferring resistance in conjugative matings with other strains of H. ducreyi and other species of Haemophilus. Restriction endonuclease digestion patterns suggest a relationship between H. ducreyi plasmids and other tetracycline resistance plasmids in Haemophilus. The presence of plasmid-mediated resistance to the tetracyclines limits the use of these agents for the treatment of chancroid.
Efficacy of 2'-nor-2'-deoxyguanosine treatment for orofacial herpes simplex virus type 1 skin infections in mice
Authors: Davies M E , Bondi J V , Field A K
Published: June 2012

2'-Nor-2'-deoxyguanosine (2'NDG), a new antiviral agent, conferred protection when given orally or topically to hairless mice after the mice were subjected to orofacial infection with herpes simplex virus type 1. The average severity of orofacial lesions was significantly reduced in mice receiving oral gavage treatments twice daily for 7 days beginning 3 h postinfection. The minimum effective dose of 2'NDG was 0.2 mg/kg per day. A minimum of eight treatments over 4 days resulted in a significant reduction in lesion severity. Topical treatment begun 3 h postinfection and continued four times daily for 3 days resulted in a minimum effective dose of 0.06%. Oral treatment with 2'NDG begun as late as 72 h postinfection or topical treatment begun as late as 48 h postinfection resulted in significantly reduced lesion severity compared with lesion severity among placebo-treated animals. In addition, significant prevention of ganglionic infection occurred when 2'NDG was administered either orally or topically within 24 h after infection.
Determination of flumequine and a hydroxy metabolite in biological fluids by high-pressure liquid chromatographic, fluorometric, and microbiological methods
Authors: Harrison L I , Schuppan D , Rohlfing S R , Hansen A R , Hansen C S , Funk M L , Collins S H , Ober R E
Published: June 2012

A sensitive and specific high-pressure liquid chromatographic method is described for the determination of the antibacterial drug flumequine and a major metabolite, 7-hydroxyflumequine, in human plasma and urine. The assay was linear over a concentration range of 1 to 120 micrograms/ml for both compounds. This method is compared with fluorometric and microbiological assays for flumequine. These latter methods did not differentiate between flumequine and any fluorescent or antimicrobiologically active metabolites. However, because essentially all drug in the plasma was found to be flumequine in radiolabeled studies, levels of unchanged drug in the plasma could be quantitated by either high-pressure liquid chromatography or fluorometry. Although only high-pressure liquid chromatography was able to specifically measure flumequine in the urine, the antimicrobial activity of the urine, which is more therapeutically relevant due to antimicrobially active metabolites, could be quantitated by either the fluorometric or the microbiological assay.
Staphylococcal endocarditis in rabbits treated with a low dose of cloxacillin
Authors: Lorian V , Zak O , Kunz S , Vaxelaire J
Published: June 2012

Rabbits with established staphylococcal endocarditis, injected twice at an interval of 2 h with either 0.5 mg of cloxacillin per kg or saline, were sacrificed 2.5 h after the second injection. Vegetations were excised, weighed, and cultured, and ultrathin sections were prepared and examined by light microscopy, transmission electron microscopy, and scanning electron microscopy. Several affected valves were examined histologically. Concentrations of cloxacillin in serum were determined 1 and 3 h after dosage. Staphylococci grown on membranes placed on agar containing 0.09 micrograms of cloxacillin per ml and in broth at the same cloxacillin concentration (one-third of the MIC) were examined by transmission electron microscopy. The mean numbers of CFU per gram of vegetations from control and treated rabbits were 2.28 X 10(10) and 1.31 X 10(10), respectively. Vegetations of treated rabbits contained staphylococci of normal size and form as well as organisms two to six times larger than normal with multiple cross walls. Larger bacterial cells were usually located in areas close to blood; cells of normal size were usually embedded in fibrin. The structures of these staphylococci and those grown on membranes in the presence of 0.09 micrograms of cloxacillin per ml were comparable but were different from those grown in broth containing this concentration of cloxacillin. Concentrations of cloxacillin in serum were 0.166 micrograms/ml at 1 h and 0.286 micrograms/ml at 3 h after dosage. The similarities in ultrastructure between staphylococci in vegetations of treated rabbits and staphylococci grown on membranes suggest that the vegetations contained approximately 0.09 micrograms of cloxacillin per g. Thus, antibiotic penetration from blood into vegetations and diffusion into fibrin were limited.
Ciprofloxacin, a quinolone carboxylic acid compound active against aerobic and anaerobic bacteria
Authors: Chin N X , Neu H C
Published: June 2012

The in vitro activity of ciprofloxacin, a quinolone-carboxylic acid derivative, was compared with those of norfloxacin, cefotaxime, cephalexin, ceftazidime, moxalactam, amoxicillin, and methicillin and other agents, as appropriate. The MICs of ciprofloxacin for 90% of members of the family Enterobacteriaceae and for Pseudomonas aeruginosa, Neisseria spp., and Bacteroides fragilis were between 0.005 and 0.8 micrograms/ml, whereas streptococci and staphylococci were all inhibited by less than or equal to 6.3 micrograms/ml. Ciprofloxacin was 4- to 32-fold more active than norfloxacin and inhibited gentamicin-, ameikacin-, cefotaxime-, and moxalactam-resistant members of the family Enterobacteriaceae and P. aeruginosa and methicillin-resistant Staphylococcus aureus. The activity of ciprofloxacin was not affected by serum but decreased in the presence of acid urine. The frequency of resistance to ciprofloxacin was between 10(-7) and 10(-9).