bluuebunny/crossref_metadata_2025 huggingface dataset:
High incidence of sensitivity to yeast killer toxins among Candida and Torulopsis isolates of human origin
Authors: Middelbeek E J , Hermans J M , Stumm C , Muytjens H L
Published: June 2012

Among yeast strains of human origin belonging to the genera Candida, Cryptococcus, Torulopsis, and Rhodotorula which were examined for killer and sensitive characteristics with killer and sensitive strains of Cryptococcus, Hansenula, Kluyveromyces, Pichia, Saccharomyces, and Torulopsis as screening organisms, a high incidence of sensitivity to killer toxins was observed within the genera Candida and Torulopsis. Of 142 strains tested, 116 strains distributed over all Candida and Torulopsis species examined were sensitive to one or more killers. Several new intergeneric killer-sensitive relationships are described. Furthermore, killing activity was exhibited by six strains of Candida (C. krusei, C. guilliermondii) and three strains of Torulopsis (T. glabrata).
Effects of tetracycline on the streptococcal flora of periodontal pockets
Authors: Hawley R J , Lee L N , LeBlanc D J
Published: June 2012

The effects of tetracycline on the subgingival streptococcal flora of periodontal patients were examined. Before antibiotic treatment, tetracycline-resistant isolates were obtained from 24 to 25 patients. In most patients, the proportion of the subgingival flora resistant to tetracycline increased after 2 weeks of therapy (1,000 mg of tetracycline/day) and then decreased after the cessation of treatment. Cultural conditions used for primary isolation were designed to favor the growth of facultative streptococci. Consequently, the majority (99%) of resistant isolates were identified as streptococci. Among 407 tetracycline-resistant Streptococcus isolates chosen for further classification, 9 species were identified, with S. sanguis (63%) and S. mitis (19%) predominating. There were no significant differences in the distribution of species isolated before and after treatment and after the cessation of tetracycline treatment. Plasmids were isolated from only 23 of 121 resistant streptococcal strains examined, suggesting that tetracycline resistance is not plasmid mediated in the majority of these oral streptococci.
Randomized trial of high- and low-dose ampicillin therapy for treatment of severe dysentery due to Shigella dysenteriae type 1
Authors: Gilman R H , Koster F , Islam S , McLaughlin J , Rahaman M M
Published: June 2012

To establish optimal therapy for severe dysentery due to Shigella dysenteriae type 1 and Shigella flexneri, we compared in a prospective randomized trial two oral ampicillin doses (50 and 150 mg/kg per day) in 57 children and 39 adults in Dacca, Bangladesh. Clinical failure did not occur in either group, indicating that conventional doses need not be increased even in severe disease. Among children 3 years of age or under, bacteriological relapses tended to be more frequent in the low-dose group and were not related to serum levels of ampicillin, nutritional status, or the severity of colitis on admission. Therefore, we recommend that younger children be treated with 100 mg/kg per day of oral ampicillin.
Comparison of in vitro activity of moxalactam (LY127935) with cefazolin, amikacin, tobramycin, carbenicillin, piperacillin, and ticarcillin against 420 blood culture isolates
Authors: Reimer L G , Mirrett S , Reller L B
Published: June 2012

To compare the in vitro activity of moxalactam (LY127935), a new broad-spectrum antimicrobial agent, with cefazolin, amikacin, tobramycin, carbenicillin, piperacillin, and ticarcillin, each drug was tested against 420 bacterial isolates from the blood of septic patients. Standard broth dilution methods were used to determine minimum inhibitory and bactericidal concentrations. LY127935 was as active as the aminoglycosides against aerobic gram-negative organisms, including Pseudomonas aeruginosa, and was at least 10-fold more active than the other beta-lactam agents against these bacteria. LY127935 was the most active agent tested against Bacteroides fragilis; its activity against all other anaerobic bacteria and Staphylococcus aureus was similar to those of the other agents tested. All streptococci, however, grew at higher concentrations of LY127935 than any other drug, and Streptococcus faecalis and Listeria monocytogenes were not inhibited at the highest concentration tested (minimum inhibitory concentration, > 64 microgram/ml). Although a greater proportion of blood culture isolates were susceptible to LY127935 than to any other drug tested, LY127935 does not have a sufficiently broad spectrum of in vitro activity to be recommended safely alone for empirical treatment of sepsis of unknown etiology.
Bioassay of antibiotics in body fluids from patients receiving cancer chemotherapeutic agents
Authors: Wright D N , Matsen J M
Published: June 2012

Patients receiving antitumor chemotherapy are at increased risk of developing nosocomial infections, and the antibacterial therapy of such infections is often monitored by bioassay. The effect of antitumor agents on seven bioassay procedures using strains of Sarcina, Klebsiella, Clostridium, Pseudomonas, Staphylococcus aureus, and S. epidermidis or Bacillus was evaluated. The minimum inhibitory concentrations of six antitumor drugs, cytarabine, dactinomycin, doxorubicin, 5-fluorouracil, methotrexate, and vinblastine, determined for each of the test organisms, showed that 5-fluorouracil, dactinomycin, and doxorubicin are used at blood levels sufficient to interfere with bioassay procedures. The other drugs have minimum inhibitory concentrations as much as 100 times the expected blood levels. Antibiotic (gentamicin, kanamycin, cephalothin, and carbenicillin) recovery experiments in the presence of therapeutic levels of antitumor agents showed no in vitro inactivation of antibiotic. However, at low cephalothin concentrations (less than 20 microgram/ml) in the presnce of 5-fluorouracil, bioassay results were in error by as much as 100%. The data indicate that bioassay procedures for the determining of antibacterial drug levels may need to be modified for those patients receiving antitumor therapy with 5-fluorouracil, doxorubicin, or dactinomycin.
Antiviral and interferon-inducing properties of interferon inducers administered with prostaglandins
Authors: Stringfellow D A
Published: June 2012

Prostaglandins enhanced the interferon response and therapeutic activity of interferon inducers in Friend leukemia virus-infected mice. A similar enhancement in interfron responsiveness but not antiviral activity was observed in mice infected with rapidly acute viruses.
Synergistic action of ampicillin and nafcillin against ampicillin-resistant Haemophilus influenzae
Authors: Yogev R , Burkholder E , Davis A T
Published: June 2012

Six strains of ampicillin-resistant Haemophilus influenzae type b were studied in vitro for synergy between ampicillin and nafcillin. The minimal inhibitory concentrations for these strains with 10(4) colony-forming units per ml were 6.25 to 12.5 microgram of ampicillin per ml and 6.25 to 25 microgram of nafcillin per ml. Studies with these agents demonstrated synergism against all six strains of H. influenzae type b. Most strains were inhibited by 0.78 microgram of nafcillin plus 0.78 microgram of ampicillin per ml. A child with osteomyelitis caused by H. influenzae type b was successfully treated with a combination of ampicillin and nafcillin. These data suggest that further studies assessing the synergistic effect of this drug combination against H. influenzae type b are warranted.
Plasma beta 2 microglobulin as a means of predicting gentamicin serum concentrations
Authors: Valsamis J , Brauman H , Yourassowsky E
Published: June 2012

A novel and accurate method for predicting gentamicin peak serum concentration is described. The method considers body weight and renal function as determined by the concentration of beta 2 microglobulin in plasma. In 32 subjects whose renal function ranged from normal to severely impaired, the peak serum concentration of gentamicin was more closely correlated with beta 2 microglobulin (r = 0.69) and with creatinine clearance (r = 0.69) than with serum creatinine (r = 0.53). A nomogram was constructed which related plasma beta 2 microglobulin concentrations and body weight to predicted gentamicin peak serum concentrations. When the nomogram was clinically applied, the predicted peak gentamicin concentrations corresponded closely to the actual measurements obtained (t = 0.64; P is not significant). We suggest that plasma beta 2 microglobulin concentrations compare favorably with serum creatinine values in the prediction of gentamicin peak concentrations in patients with renal impairment.
Preparation and properties of liposome-associated gentamicin
Authors: Morgan J R , Williams K E
Published: June 2012

Gentamicin was successfully incorporated into neutral, anionic, and cationic liposomes, and the percentage of gentamicin incorporated was found to be a function of lipid concentration. Gentamicin did not leak out of the liposomes over a 3-week period at 4 degrees C. When liposome-associated gentamicin was administered intravenously to rabbits, its serum half-life was greatly prolonged. Intragastric administration of dipalmitoylphosphatidylcholine liposomes containing gentamicin resulted in the appearance of gentamicin in serum. Liposome-associated gentamicin, when administered intravenously, led to the appearance of gentamicin in the liver and spleen, which was not observed when rabbits were injected with free gentamicin.
Comparison of amoxicillin and ampicillin activities in a continuous culture model of the human urinary bladder
Authors: Anderson J D , Johnson K R , Aird M Y
Published: June 2012

Sixteen isolates of Escherichia coli were obtained from women with significant acute urinary tract infections who were subsequently treated with amoxicillin. The activities of amoxicillin and ampicillin against these organisms were compared in urine in a continuous culture apparatus which partly simulated the milieu of the human urinary bladder. After introduction of amoxicillin into the bladder model, mean viable counts for 14 susceptible strains (minimum inhibitory concentration less than or equal to 32 microgram/ml) at 10, 20, 30, and 45 min fell to 34, 8, 0.4, and 0.2% of the original. Corresponding figures for ampicillin were 56, 24, 11, and 2.4%. Viable counts obtained at seven timed intervals up to 2 h were significantly (P = 0.025) lower with amoxicillin than ampicillin. Both antibiotics had a similar activity in conventional disk susceptibility and surface plate minimum inhibitory concentration tests. The realism of the model was confirmed by comparing response to amoxicillin in vivo and in vitro. A serious discrepancy was seen in only one of the 16 cases.
Combination chemotherapy: interaction of 5-methoxymethyldeoxyuridine with adenine arabinoside, 5-ethyldeoxyuridine, 5-iododeoxyuridine, and phosphonoacetic acid against herpes simplex virus types 1 and 2
Authors: Ayisi N K , Gupta V S , Meldrum J B , Taneja A K , Babiuk L A
Published: June 2012

The antiviral activity of 5-methoxymethyl-2'-deoxyuridine (MMUdR) was compared with that of 5-iodo-2'-deoxyuridine (IUdR), 5-ethyl-2'-deoxyuridine (EtUdR), adenine arabinoside (Ara-A), and phosphonoacetic acid (PAA) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). MMUdR was more potent than Ara-A and PAA but less active than EtUdR and IUdR against HSV-1 in rabbit kidney (RK-13) cells. In Vero cells, the antiviral activities of MMUdR, Ara-A, and PAA against HSV-1 were of the same order of magnitude. The antiviral potency against HSV-2 varied with the strain of virus used. All strains of HSV-2 were markedly inhibited by EtUdR and IUdR and to a lesser degree by PAA. However, considerable variation was noticed in the susceptibility of HSV-2 strains to Ara-A and MMUdR. Interaction of MMUdR with Ara-A, EtUdR, IUdR, and PAA was investigated by the method of response isobolograms. MMUdR showed synergistic activity in combination with Ara-A and PAA but antagonistic activity in combination with EtUdR and IUdR against herpesviruses. Minimum toxic dose (concentration required to produce definite evidence of microscopic cytotoxicity in rapidly growing RK-13 cells) was determined for each compound and was found to be 512, 172, 64, 8, and less than 0.5 microgram/ml for MMUdR, PAA, Ara-A, EtUdR, and IUdR, respectively. MMUdR was found to have the maximum antiviral index against HSV-1 (512) and HSV-2 strains X-265 (102) and ATCC (85). Antiviral index was defined as the minimum toxic dose divided by the dose that reduced plaque numbers by 50%.
Effect of protein binding on the penetration of nonmetabolized cephalosporins into atrial appendage and pericardial fluids in open-heart surgical patients
Authors: Nightingale C H , Klimek J J , Quintiliani R
Published: June 2012

At various times before surgery, 33 patients undergoing coronary artery bypass or cardiac valve replacement surgery received a single 2.0-g dose of either cefazolin or cephradine. Simultaneous single serum, atrial appendage, and pericardial fluid samples were obtained from the patients at various times and analyzed for drug content. Compared with cephradine, cefazolin yielded higher total serum, atrial appendage, and pericardial fluid levels. Unbound (free) levels of cephradine in serum and pericardial fluid were, however, higher than those of cefazolin. It remains uncertain whether the higher and more prolonged total levels of cefazolin in the right atrial appendage and in serum, or the higher free levels of cephradine in pericardial fluid and in serum, provide either one with a therapeutic advantage.
High-pressure liquid chromatography analysis and single-dose disposition of tobramycin in human volunteers
Authors: Haughey D B , Janicke D M , Adelman M , Schentag J J
Published: June 2012

A sensitive and specific fluorometric high-pressure liquid chromatography technique was developed to measure both tobramycin and an internal standard (gentamicin C2). The assay utilizes direct extraction of the o-phthalaldehyde derivatives from serum and urine. Coefficients of variation were 7.9% (serum) and 6.0% (urine) at a tobramycin concentration of 1.0 microgram/ml. The lower limit of assay sensitivity was 0.2 microgram/ml. Results obtained from high-pressure liquid chromatography were in excellent agreement with those from radioimmunoassay for both serum (r = 0.97) and urine (r = 0.91). No other aminoglycoside antibiotics and no other antibiotics that were tested caused interfering peaks. Tobramycin (1 mg/kg intravenous bolus) was administered to three healthy volunteers. Tobramycin concentrations were detectable for 10 h in serum and for 240 h in urine after a 1-mg/kg intravenous dose. A two-compartment pharmacokinetic model was required to describe the tobramycin disposition. Urinary recovery of tobramycin over a 10-day period accounted for 95.8, 94.3, and 83.1% of the administered dose. High-pressure liquid chromatography methodology is sufficiently sensitive to determine single-dose, two-compartment tobramycin pharmacokinetics from urinary excretion data, thus verifying the prolonged excretion of tobramycin after a single dose. The analytical methodology and pharmacokinetic techniques described may be useful in studying other aminoglycosides.
L-lysine epsilon-aminotransferase involved in cephamycin C synthesis in Streptomyces lactamdurans
Authors: Kern B A , Hendlin D , Inamine E
Published: June 2012

In Streptomyces lactamdurans, the precursor of the alpha-aminoadipoyl side-chain of cephamycin C is L-lysine. In this regard, streptomycetes differ strikingly from the fungi, which produce alpha-aminoadipic acid during the synthesis, rather than the breakdown, of L-lysine. Studies using a cell-free system showed that an aminoadipic acid. The product of this reaction was trapped and subsequently purified by ion-exchange chromatography. Thin-layer chromatography, spectrophotometry, and amino acid oxidase digestion studies identified the reaction product as L-1-piperideine-6-carboxylate, implying enzymatic removal of the epsilon amino group of L-lysine. This enzymatic activity (E.C. 2.6.1.36; L-lysine: 2-oxoglutarate 6-aminotransferase) is highly unusual and was previously conclusively demonstrated only in the genus Flavobacterium. In S. lactamdurans, the specific activity of this enzyme reaches a peak early in the fermentation (approximately 20 h) and decreases as the antibiotic begins to appear.
Effects of ribavirin on respiratory syncytial virus in vitro
Authors: Hruska J F , Bernstein J M , Douglas R G , Hall C B
Published: June 2012

Ribavirin was demonstrated to have an antiviral effect on respiratory syncytial virus in vitro. A 50% reduction in plaque number was observed at concentrations of 3 or 10 micrograms of ribavirin per ml. This effect was observed when the drug was added as late as 12 h postinfection. At concentrations of greater than 10 micrograms of ribavirin per ml, the size of the syncytial plaque also noticeably decreased. Ribavirin similarly decreased the number of infectious units released into the culture supernatant. The antiviral effect was observed to be inversely related to the size of the viral inoculum, although all concentrations above 3.2 micrograms of ribavirin per ml visibly lessened the cytopathic effect regardless of the inoculum. Cloning of respiratory synctial virus in inhibitory concentrations of ribavirin failed to show increased resistance to the drug.
GR 20263, a new broad-spectrum cephalosporin with anti-pseudomonal activity
Authors: O'Callaghan C H , Acred P , Harper P B , Ryan D M , Kirby S M , Harding S M
Published: June 2012

GR 20263 is a new broad-spectrum injectable cephalosporin which is stable to most beta-lactamases. Its in vitro activities were of the same order as those of cefotaxime against most gram-negative bacteria, were clearly inferior to cefotaxime against Staphylococcus aureus, but were significantly more active against Pseudomonas aeruginosa. Against the 25 strains used, GR 20263 was significantly more active than any of the other agents tested: piperacillin, azlocillin, gentamicin, amikacin, and carbenicillin. GR 20263 protected mice against experimental infections with P. aeruginosa more effectively than other beta-lactam antibiotics; its general effectiveness in this test was comparable with gentamicin. Studies on human volunteers showed that it produces high, long-lasting blood levels, with much of the antibiotic being recovered in the urine. Intramuscular and intravenous injections were well tolerated by the volunteers, and there were no untoward side effects.
Anesthetic action and virus replication: inhibition of measles virus replication in cells exposed to halothane
Authors: Knight P R , Nahrwold M L , Bedows E
Published: June 2012

Replication of measles virus in BSC cells was studied in the presence of halothane, a commonly used volatile anesthetic. At clinical concentrations of the anesthetic, appearance of progeny virus was decreased in a dose-related manner. This inhibition was reversible as the removal of halothane allowed virus replication to be resumed. Studies attempting to elucidate the mechanism of action of the anesthetic inhibition of virus replication revealed that halothane did not directly inactivate the virus particle or prevent viral adsorption to the cell. Infectious virus and nucleocapsid production were decreased or stopped, depending on the anesthetic dosage used. Direct immunofluorescent staining for measles virus antigen was negative in cells treated at the higher concentrations of halothane. Recovery of nucleocapsid production started within a few hours after removal of halothane. Furthermore, the combined inhibitory effects on viral ribonucleic acid synthesis of 5-azacytidine and halothane were additive. This evidence suggests that inhibition of measles virus replication occurs at or before ribonucleic acid synthesis.
Failure of single doses of cefazolin and cefamandole to penetrate experimental chronic Escherichia coli abdominal abscesses
Authors: Gerding D N , Kozak A J , Peterson L R , Hall W H
Published: June 2012

Four perforated capsules were implanted into the abdominal cavity of each of three rabbits. After 4 to 5 weeks, single doses of cefazolin (30 mg/kg) or cefamandole (90 mg/kg) were administered intramuscularly. Peak levels of the respective drugs in serum were 104 +/- 10 and 127 +/- 5 micrograms/ml (mean +/- standard error); corresponding peak levels in capsule fluid were 6.3 +/- 2.3 micrograms/ml. Sixteen weeks after implantation, 2 X 10(6) colony-forming units of a strain of Escherichia coli susceptible to cefazolin (minimum inhibitory concentration, 1.0 microgram/ml) and cefamandole (minimum inhibitory concentration, less than 0.125 microgram/ml) was introduced into each of the 12 capsules. Chronic infection was established in seven of the capsules. At 4 to 6 weeks after infection, cefazolin and cefamandole were again administered. Peak serum concentrations were 102 +/- 3.3 micrograms/ml for cefazolin and 148 +/- 6.7 micrograms/ml for cefamandole. Peak concentrations in noninfected capsules were 7.5 +/- 3.4 and 12.1 +/- 2.1 micrograms/ml, respectively, not statistically different from the first study (P greater than 0.2). However, peak concentrations in infected capsules (less than 0.3 microgram/ml) were strikingly lower than in uninfected capsules (P less than 0.002). In keeping with the latter finding, quantitative cultures of E. coli in the infected capsules remained unchanged. Administration of [14C]cefamandole indicated that low drug levels were a result of poor drug penetration rather than drug inactivation or binding. Lack of vascularity and capsule wall necrosis may be responsible for poor drug penetration.
Antiherpesviral activity and inhibitory action on cell growth of 5-alkenyl derivatives of 1-beta D-arabinofuranosyluracil
Authors: Machida H , Kuninaka A , Yoshino H , Ikeda K , Mizuno Y
Published: June 2012

Antiherpesviral activity of 5-vinyl-1-beta-D-arabinofuranosyluracil was as high as that of 1-beta-D-arabinofuranosylthymine, whereas the former was less inhibitory to cell growth than the latter. 5-Propenyl- and 5-butenyl-1-beta-D-arabinofuranosyluracil were less active than 5-vinyl-1-beta-D-arabinofuranosyluracil.
Effect of pancreatitis on ampicillin excretion in pancreatic fluids of dogs
Authors: Rubinstein E , Haspel J , Klein E , Ben-Ari G , Schwarzkopf R , Tadmor A
Published: June 2012

Pancreatic excretion of ampicillin was evaluated in normal dogs and in dogs with induced pancreatis. A 100-mg/kg ampicillin dose administered intravenously induced mean peak serum levels of 100 micrograms/ml, and a 200-mg/kg intravenous dose induced a mean peak serum level of 273 microgram/ml. Ampicillin serum levels did not differ between the group of normal dogs and those with pancreatitis. In normal dogs, the peak pancreatic fluid ampicillin concentration after the 100-mg/kg dose was 0.4 microgram/ml, and that after the 200-mg/kg dose was 2.7 micrograms/ml. In dogs with pancreatitis, the mean peak ampicillin concentration in the pancreatic fluid after the 100 mg/kg dose was 19 micrograms/ml, and that after the 200-mg/kg dose was 38.5 micrograms/ml. Pancreatic fluid ampicillin concentrations were therapeutic in dogs with pancreatitis and subtherapeutic in normal dogs.
Susceptibilities of anaerobic bacteria to cefoperazone and other antibiotics
Authors: Kaye D , Kobasa W , Kaye K
Published: June 2012

Two hundred fifty clinical isolates of anaerobic bacteria were tested for suceptibility to cefoperazone, cefamandole, cefoxitin, carbenicillin, clindamycin, and chloramphenicol. Anaerobic gram-positive cocci were susceptible to all of the antibiotics tested. Clindamycin was the most active agent against Bacteroides species, followed by chloramphenicol and then cefoxitin. Cefoperazone was less active than cefoxitin and equal in activity to carbenicillin. Cefamandole was the least active antibiotic against Bacteroides. B. distasonis, B. vulgatus, B. thetaiotaomicron, and B. ovatus were more resistant to the antibiotics than B. melaninogenicus, B. oralis, or B. bivius. Clindamycin was the most active agent against Clostridium species, followed by chloramphenicol; the three cephalosporins and carbenicillin were about equal in activity. Clindamycin was the most active antibiotic against Fusobacterium species, followed by chloramphenicol, carbenicillin, and cefoperazone (which were about equally active) and then cefamandole.
Metronidazole in treatment against Haemophilus vaginalis (Corynebacterium vaginale)
Authors: Ralph E D , Amatnieks Y E
Published: June 2012

The rate of bactericidal activity and inactivation of metronidazole was studied in time-kill curves with Haemophilus vaginalis (Corynebacterium vaginale). The minimum inhibitory concentrations of metronidazole for the eight strains tested ranged from 4 to 16 micrograms/ml. At a concentration of 20 micrograms/ml, metronidazole demonstrated a slow cidal effect against exponential-phase organisms, requiring 24 to 48 h for completion. Inactivation of metronidazole during the time-kill curve was quite variable and averaged 28% of the starting concentration after 48 h. Against stationary-phase organisms (inoculum, 10(10) to 10(11) colony-forming units per ml), a slow cidal effect was also seen, with an average inactivation of metronidazole of 38% after 48 h. At a subinhibitory concentration of 5 micrograms/ml, metronidazole was inactivated to the greatest degree (57% after 48 h). Therefore, in contrast to earlier studies in which metronidazole was rapidly and consistently cidal within 4 h against obligate anaerobes and was almost completely inactivated by 8 h, the bactericidal effect of metronidazole againsts H. vaginalis in this study was much slower and was associated with a variable and slower rate of inactivation.
Examination of parameters affecting human interferon production with microcarrier-grown fibroblast cells
Authors: Giard D J , Fleischaker R J
Published: June 2012

Various parameters were examined for their effects on interferon production with human fibroblast cells (FS-4) grown on microcarriers, using a superinduction procedure. Optimal concentrations of cycloheximide and actinomycin D during induction were 10 micrograms/ml, respectively. Cells required 5 to 6 h of exposure to cycloheximide and at least 2 h of exposure to actinomycin D to achieve maximum yields. FS-4 cells were found to grow well at low serum concentrations (2.5 and 5%) and actually produced higher yields of interferon than cells grown at higher serum concentration (10 and 20%). Kinetics of interferon production at various temperatures revealed that significantly higher yields could be obtained at 34 degrees C than at either 37 or 30 degrees C. Priming cells for 16 h with 50 U of interferon per ml resulted in consistently higher yields of interferon. By modifying the superinduction procedure in accordance with the above findings, it is now possible to consistently obtain interferon yields of greater than 20,000 international units per 10(6) cells.
Direct-current bactericidal effect on intact skin
Authors: Bolton L , Foleno B , Means B , Petrucelli S
Published: June 2012

Positive carbon-containing electrodes conveying 5 or more microA of constant direct current per cm2 showed bactericidal activity on intact back skin of 13 human subjects. This effect increased with the duration of stimulation up to a total surface bacterial kill at 20 h. When total current and current density were varied independently on 16 sites on the backs of eight subjects, the effect was dependent on current density, not on total current. Electrodes driven by similar voltages but which removed the electrochemical reaction from inoculated sites on the backs of three subjects failed to reduce the numbers of colony-forming units as compared with those sampled from control sites. This showed the bactericidal effect to be electrochemical in origin, probably mediated by local acidity generated at the surface of the positive carbon-containing electrodes. With an adhesive tape stripping technique on three sites on each of six subjects, it was determined that the effect extended into the epidermis of the human back. No effect was observed beneath negative or control electrodes under the same conditions.
Ineffectiveness of adenine arabinoside and adenine arabinoside 5'-monophosphate in simian varicella infection
Authors: Soike K F , Felsenfeld A D , Gibson S , Gerone P J
Published: June 2012

Adenine arabinoside and adenine arabinoside 5'-monophosphate (ara-AMP) have been evaluated for antiviral activity against simian varicella virus infection in monkeys. In a preliminary study for toxicity, intramuscular injection of ara-AMP at 15 mg/kg per day as a single injection for 5 days to two normal patas monkeys caused no detectable local reaction, no weight loss or changes in serum transaminase levels, and no hematological abnormalities. When this dose was given in the treatment of four simian varicella virus-infected patas monkeys, no effect was observed on the clinical course of infection, as compared with four infected monkeys which received phosphate-buffered saline. Treatment was begun 43 h after virus inoculation and was continued for 16 days. Toxicity of intravenously administered ara-AMP at 100 to 50 mg/kg per day for 5 days to pairs of uninfected patas monkeys was evident by hematological and hepatic histological alterations, as well as the death of one monkey in each pair. No gross evidence of toxicity occurred in two monkeys which received 20 mg of ara-AMP per kg per day. The antiviral efficacy of intravenous treatment was studied in groups of four African green monkeys which received adenine arabinoside at 15 mg/kg per day or ara-AMP at 18.4 mg/kg per day. Drug administration began 48 h after inoculation with simian varicella virus and continued for 10 days. The monkeys that received treatment did not respond to infection differently from four infected control monkeys similarly treated with phosphate-buffered saline.
Comparative bactericidal effects of azlocillin and ticarcillin against Pseudomonas aeruginosa
Authors: White A R , Comber K R , Sutherland R
Published: June 2012

Azlocillin was relatively ineffective against actively growing cultures of Pseudomonas aeruginosa in tests of bacteriolytic and bactericidal activity in which ticarcillin demonstrated pronounced bactericidal effects over a wide range of concentrations. Microscopic observation showed that azlocillin generally induced the formation of filamentous cells of P. aeruginosa which lysed only slowly, but ticarcillin caused the production of spheroplasts and subsequent rapid lysis. During the course of the bactericidal tests, azlocillin was inactivated, presumably by the beta-lactamase produced by P. aeruginosa, and the filamentous cells resumed normal cell division and growth. In contrast, there was no loss of ticarcillin activity, and there was no evidence of resumption of growth of P. aeruginosa in the presence of ticarcillin. These results suggest that the different bactericidal effects demonstrated by azlocillin and ticarcillin against P. aeruginosa are related primarily to dose-related differences in inhibition of cell wall synthesis and secondarily to the instability of azlocillin to pseudomonal beta-lactamase.
In vitro susceptibility testing of Paracoccidioides brasiliensis to sulfonamides
Authors: Restrepo A , Arango M D
Published: June 2012

A total of 60 clinical isolates of Paracoccidioides brasiliensis were tested for susceptibility to sulfadiazine and sulfadimethoxyne by the agar dilution technique. A modification of the Mueller-Hinton medium was devised which gave good growth of the yeast form. The minimum inhibitory concentrations for only 51.6% of the isolates were in the range of the recommended blood serum concentration (50 micrograms/ml). For 6 to 8% of the isolates, the minimum inhibitory concentrations were above 200 micrograms of both sulfadiazine and sulfadimethoxyne per ml. A significant decreases in susceptibility was demonstrated for one isolate obtained from a patient relapsing during sulfonamide therapy.
Streptococcus faecium-derived antibacterial substance antagonistic to Bifidobacteria
Authors: Harasawa R , Suzuki K , Mitsuoka T
Published: June 2012

An antagonistic strain of Streptococcus faecium was isolated from human feces, and it displayed a marked inhibition of bifidobacteria on agar plates. In liquid culture this isolate produced an antibacterial substance that can be partially purified by ammonium sulfate precipitation followed by gel filtration and ion-exchange chromatography. Its activity was assayed by the inhibition of growth of Bifidobacterium longum. The substance was sensitive to digestion by proteolytic enzymes and alpha-amylase, but was resistant to treatment with 6 M urea, dithiothreitol, 2-mercaptoethanol, ethyl ether, chloroform, and lysozyme. It was also stable to heating at 100 degrees C for 60 min. Its molecular weight was estimated to be about 50,000 by gel filtration.
Biliary elimination of mezlocillin: an experimental and clinical study
Authors: Brogard J M , Kopferschmitt J , Arnaud J P , Dorner M , La Villaureix J
Published: June 2012

The biliary elimination of mezlocillin, a new semisynthetic penicillin of the acyl-ureido-penicillin group, was investigated in vitro in rabbit liver preparations and in vivo in humans. Experimentally, mezlocillin recovery in the bile during perfusion of isolted rabbit liver (3 h; n = 5) averaged 20.3% of the administrered dose (10 mg). The mean peak concentration in the bile (758 +/- 129.3 micrograms/ml) was reached between 0.5 and 1 h. Biliary clearance was 169 ml/h. In healthy subjects (n = 5), the concentrations of antibiotic measured in the duodenal fluid during a period of 4 h after intravenous administration of 5 g of mezlocillin ranged between 440 and 637 micrograms/ml. In 10 cholecystectomized patients provided with a T-tube, intramuscular injection of 1 g of mezlocillin resulted in a biliary peak concentration of 295.7 +/- 58.1 micrograms/ml. Mean total amount of antibiotic eliminated in the bile over 12 h corresponded to 2.6% of the administered dose. Assays performed during surgery after intravenous administration of 2 g of mezlocillin (n = 10) showed antibiotic activity of 895 +/- 196 micrograms/ml in the common duct bile and 402 +/- 133 micrograms/ml in the gallbladder bile. These data were compared with the values determined for 11 other beta-lactamines studied under identical conditions.
Classification of polyene antibiotics according to their synergistic effect in combination with bleomycin A2 or fusidic acid
Authors: Akiyama S , Tabuki T , Kaneko M , Komiyama S , Kuwano M
Published: June 2012

Five polyene antibiotics were compared for their effects on colony formation of either Chinese hamster V79 or Saccharomyces cerevisiae cells. A 10 to 40 times higher concentration of amphotericin B (heptaene) or nystatin (degenerated heptaene) was necessary to inhibit colony formation of hamster cells than that needed to inhibit colony formation of yeast cells. In contrast, colony formation of both hamster and yeast cells was inhibited to the same extent by similar concentrations of filipin (pentaene), pentamycin (pentaene), or pimaricin (tetraene). The five polyene antibiotics were also compared for their effects on colony formation of either V79 or S. cerevisiae cells when combined with a nonpolyene antibiotic, fusidic acid or bleomycin A2. Amphotericin B or nystatin could augment the cytocidal effect of fusidic acid but not that of bleomycin A2, whereas pentamycin or pimaricin could augment the cytocidal effect of both fusidic acid and bleomycin A2 against hamster and yeast cells. Filipin was found to enhance the action of fusidic acid and bleomycin upon growth of mammalian cells, whereas the pentaene polyene significantly potentiated the action of fusidic acid, but not that of bleomycin A2, against S. cerevisiae. It was therefore suggested that these polyene antibiotics be classified into two groups: group 1 (pimaricin, pentamycin, and filipin) and group 2 (amphotericin B and nystatin).
Antimycoplasmal activity of dimethylphenols in a tracheal explant culture system
Authors: Agee C C , Engelhardt J A , Gabridge M G
Published: June 2012

Mycoplasma pneumoniae induces pneumonia-like symptoms in hamsters and causes ciliostasis and cytonecrosis in hamster tracheal explants. 2,4-Dimethylphenol and, to a lesser extent, its 2,3-, 2,5-, and 2,6-dimethylphenol isomers protected tracheal explants from these changes after exposure to virulent M. pneumoniae strain PI 1428. The effect was concentration, time, and isomer dependent. At concentrations of 10(-9) M or greater, 2,4-dimethylphenol completely prevented the morphological (loss of ciliated cells) and biochemical (decreased dehydrogenase activity) changes normally observed after exposure to M. pneumoniae. Apparently, 2,4-dimethylphenol interfered with an early event in the infection process. Complete protection required that it be present during the first 2 h of exposure of the explants to the infecting mycoplasmas. These xylenols may prove to be useful tools for helping to define the mechanisms of pathogenesis in certain respiratory infections.
Substrate-labeled fluorescent immunoassay for amikacin in human serum
Authors: Thompson S G , Burd J F
Published: June 2012

A homogeneous substrate-labeled fluorescent immunoassay has been developed to measure amikacin levels in human serum. Amikacin is covalently labeled with the fluorogenic enzyme substrate beta-galactosyl-umbelliferone. This beta-galactosyl-umbelliferone-amikacin conjugate is nonfluorescent under assay conditions until it is hydrolyzed by beta-galactosidase to yield a fluorescent product. When antiserum to amikacin binds the substrate-labeled drug, the antibody complex formation inhibits hydrolysis of the fluorogenic substrate. Reaction mixtures containing a constant level of substrate-labeled amikacin and a limiting amount of antiserum enable labeled and unlabeled amikacin to compete for the antibody-binding sites. Unbound substrate-labeled drug is hydrolyzed by the enzyme to release a fluorescent product that is proportional to the unlabeled amikacin concentration. The amikacin levels found in clinical serum samples with this method were comparable (r = 0.987) to those obtained by radioimmunoassay. The fluorescent immunoassay is rapid and simple to perform and requires only 2 microliters of serum.
Antiviral activity of antilipidemic compounds on herpes simplex virus type 1
Authors: Mehl J K , Witiak D T , Hamparian V V , Hughes J H
Published: June 2012

Two antilipidemic compounds, clofibrate and procetofene, inhibited the replication of herpes simplex virus type 1 (HSV-1) in African green monkey kidney cells. Clofibrate, at a concentration of 400 mumol/liter caused a 63% reduction (P < 0.001) in HSV-1 yield and at 100 mumol/liter caused a 62% reduction (P < 0.001) in plaque formation. Two stereoisomeric analogs of clofibric acid, (-)- and (+)-desmethyl clofibric acid, also caused a significant inhibition of HSV-1 replication. Procetofene at 5 mumol/liter caused a 56% reduction (P < 0.001) in HSV-1 plaques and at 10 mumol/liter caused a significant reduction (P < 0.001) in both viral yield (42 to 54%) and plaque formation (65%). Procetofene also inhibited the development of HSV-1 plaques. A concentration of 5 mumol/liter resulted in a 26% reduction (P < 0.001) in plaque diameter. Because of their nonspecific inhibitory effect on the uptake of cellular macromolecular precursors for nucleic acid and protein biosynthesis, these antilipidemic compounds may exert their antiviral activity by affecting one or more key metabolic host cell pathways.
Effects of steroid hormones on Neisseria gonorrhoeae
Authors: Lysko P G , Morse S A
Published: June 2012

Various steroids were tested for their effects upon gonococcal O2 consumption and glucose catabolism. The ability to inhibit gonococcal O2 uptake appeared to be related to the molecular configuration of the steroid. The presence of lipophilic groups enhanced inhibition, whereas the addition of hydrophilic groups markedly diminished inhibition. Steroid inhibition decreased with an increasing number of polar groups. Glucose catabolism was inhibited by steroid hormones, and the degree of inhibition was influenced by pH and medium composition. Changes in growth medium and pH also resulted in differential steroid inhibition of O2 uptake. Under certain conditions, lactate partially relieved this inhibition. Gonococci that were grown in one environment and shifted to a new environment were inhibited by steroids to the same extent as if they had been originally grown in the new environment. The differential effects of medium and pH upon steroid inhibition may be due to structural rearrangements involving membrane phase transitions or to altered receptor affinity.
Potential of mezlocillin as empiric single-agent therapy in febrile granulocytopenic cancer patients
Authors: Wade J C , Schimpff S C , Newman K A , Fortner C L , Moody M R , Young V M , Wiernik P H
Published: June 2012

Mezlocillin was used as an initial empiric antibiotic therapy for febrile (> 101 degrees F, ca. 38.33 degrees C) granulocytopenic (< 1,000/microliter) cancer patients. Patients known to be colonized with an organism resistant to 100 micrograms of mezlocillin per mol were excluded. The initial 25 cases (23 patients) received intravenous mezlocillin, 260 mg per kg per day in six divided doses; the mean 1-h-postinfusion serum level was 69 micrograms/ml. Because of the low serum level, the next 25 cases (22 patients) received 450 mg/kg per day, also in six divided doses, resulting in a mean 1-h-postinfusion serum level of 161 micrograms/ml. Both dosage regimens provided similar efficacy. Combined results show that 11 of 21 microbiologically documented infections and 7 of 13 clinically documented infections improved. Instances of bacteremia (number of cases in parentheses) were caused by Pseudomonas aeruginosa (two), Staphylococcus epidermidis (two), Clostridia perfringens (one), and Bacillus species (one); only one case improved. A rise in granulocyte count to > 500/microliters, a serum bactericidal activity of greater than or equal to 1:8 against the infecting pathogen, or both were indicators of a good therapeutic response. Despite exclusion of patients known to be previously colonized with mezlocillin-resistant organisms, 7 of 23 pathogens required a minimal concentration of greater than or equal to 100 micrograms of mezlocillin per ml for inhibition. In addition, surveillance cultures from 18 cases showed resistant organisms colonizing the gingiva, rectum, or both. Side effects of mezlocillin were minimal and included pseudoproteinuria, asymptomatic transient rise in bilirubin, and easily reversible kypokalemia. Mezlocillin, a new semisynthetic penicillin with little toxicity, was found to be inadequate as a single-agent empiric antibiotic therapy for febrile, granulocytopenic cancer patients.
Phlebitis induced by parenteral treatment with flucloxacillin and cloxacillin: a double-blind study
Authors: Svedhem A , Alestig K , Jertborn M
Published: June 2012

Two studies were performed on a total of 54 patients with staphylococcal infections. Study I compares with phlebitogenic properties of flucloxacillin after intravenous infusions when either saline or sterile water was used as a solvent. No difference was observed between the two solvents, and the frequency of phlebitis for the total material without respect to solvents was 5% after 1 day of treatment and 13% after 2 days. Study II was a double-blind comparison of phlebitis caused by intravenous infusions of either flucloxacillin or cloxacillin. The frequencies of phlebitis were found to be 18 and 13%, respectively. After 2 days of treatment the frequency of phlebitis increased dramatically for both drugs. All infusions were given through a plastic cannula of 5-cm length and 1.2-mm diameter.
In vitro activity of Ro 13-9904, cefuroxime, cefoxitin, and ampicillin against Neisseria gonorrhoeae
Authors: Yoshikawa T T , Shibata S A , Herbert P , Oill P A
Published: June 2012

In vitro susceptibilities of 87 isolates of non-penicillinase-producing Neisseria gonorrhoeae and 8 isolates of penicillinase-producing N. gonorrhoeae to Ro 13-9904, cefuroxime, cefoxitin, and ampicillin were determined. Ro 13-9904 was the most effective of the four drugs, inhibiting growth of both non-penicillinase-producing and penicillinase-producing N. gonorrhoeae.
New in vitro kinetic model for evaluating bactericidal efficacy of antibiotics
Authors: Murakawa T , Sakamoto H , Hirose T , Nishida M
Published: June 2012

A new in vitro model was devised for evaluating the bactericidal activity of antibiotics under dynamic conditions. This model accurately reproduced the observed serum levels of antibiotics after intravenous dosing. The apparatus consists of two vessels which correspond to the central and peripheral compartments of a two-compartment open model. The volume of medium in each vessel and flow rates of media were determined from the pharmacokinetic parameters calculated from the observed serum levels selected for simulation. The bactericidal activity of cefazolin against strains of Escherichia coli and Klebsiella pneumoniae showing different minimal inhibitory concentrations was investigated with the apparatus simulating serum levels after intravenous injection, and the bactericidal activity was evaluated with respect to the relationship between the minimal inhibitory concentration and the serum levels.
Cell-free cyclization of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine to isopenicillin N
Authors: Sawada Y , Baldwin J E , Singh P D , Solomon N A , Demain A L
Published: June 2012

Cell-free cyclization of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine to isopenicillin N by lytic enzyme extracts of Cephalosporium acremonium M-0198 was stimulated by ferrous ions. The optimum concentration of FeSO4 was 80 microM. No additional stimulation was observed with ascorbate, adenosine 5'-triphosphate, or alpha-ketoglutarate, but Triton X-100 and sonication of the extracts increased activity. ZnSO4 was very inhibitory to enzyme activity; CuSO4 was somewhat less inhibitory, and the least effective of the three was MnCl2. The dimer of the tripeptide was converted to a penicillin that has the biological spectrum of isopenicillin N, and this reaction was also stimulated by FeSO4. We found that sonication can be used directly to prepare extracts with cyclization activity from mycelia, without preparing protoplast lysates. The kinetics of cyclase appearance and disappearance during fermentation were similar to those of ring-expansion activity, i.e., enzyme appeared and peaked 13 h after growth ceased and then disappeared.