bluuebunny/crossref_metadata_2025 huggingface dataset:
Surveillance of Gentamicin-Resistant Gram-Negative Bacilli in a General Hospital
Authors: Kauffman Carol A. , Ramundo Nancy C. , Williams Stanley G. , Dey Chitta R. , Phair John P. , Watanakunakorn Chatrchai
Published: June 2012

Aerobic gram-negative bacilli isolated from clinical specimens from 1 January to 31 December 1976 were tested for gentamicin and tobramycin resistance by standardized disk testing. For
Pseudomonas
isolates, gentamicin resistance was 17.1% and tobramycin resistance was 2.8%. For other gram-negative bacilli, gentamicin resistance was 5.5% and tobramycin resistance was 5.4%. Seventy-four patients from whom gentamicin-resistant organisms were isolated from 1 January to 30 June 1976 were studied prospectively. These patients were elderly, had serious underlying diseases, and had received prior antibiotic therapy. Eleven patients carried gentamicin-resistant organisms at the time of transfer to our hospital from community hospitals or nursing homes. Of the 82 isolates from these 74 patients, 52 were from the urine.
Pseudomonas
was found most frequently (32 isolates), followed by
Klebsiella
(15 isolates),
Enterobacter
(10 isolates),
Serratia
(10 isolates), and
Proteus
(9 isolates). Only 3 of 32
Pseudomonas
isolates caused symptomatic infection, while 16 of 50 other gram-negative bacilli were responsible for symptomatic infection. Although amikacin was the most active drug against gentamicin-resistant gram-negative bacilli and had not been used in our hospital at the time of this study, 25% of
Pseudomonas
and 18% of all gram-negative bacilli showed resistance to this aminoglycoside.
Infection in Acute Leukemia Patients Receiving Oral Nonabsorbable Antibiotics
Authors: Hahn Davis M. , Schimpff Stephen C. , Fortner Clarence L. , Smyth A. Collier , Young Viola Mae , Wiernik Peter H.
Published: June 2012

During a 20-month period all acute nonlymphocytic patients (87 patient trials) receiving cytotoxic chemotherapy were placed on an oral nonabsorbable antibiotic regimen consisting of gentamicin, vancomycin, and nystatin in addition to an intensive program of infection prevention aimed at reducing exogenously acquired and body-surface potential pathogens. Although side effects of anorexia, diarrhea, and nausea were common, gentamicin-vancomycin-nystatin was ingested 80% of the study time. Microbial growth in gingival and rectal cultures was substantially reduced. The incidence of bacteremias and other serious infections was low.
Pseudomonas aeruginosa
, other gram-negative bacilli, and
Candida
species caused few infections along the alimentary canal, whereas infections of the skin (especially
Staphylococcus aureus
) were not reduced compared with those occurring in former years. A total of the 104 acquired gram-negative bacilli were gentamicin resistant; 5 subsequently caused infection. Thus, despite certain definite drawbacks, the use of oral nonabsorbable antibiotics to suppress alimentary tract microbial flora in combination with other infection prevention techniques in granulocytopenic cancer patients has proven feasible and tolerable and has been associated with a low order of life-threatening infections.
Biological Effects of 5-Carboxy-2′-Deoxyuridine: Hydrolysis Product of 5-Trifluoromethyl-2′-Deoxyuridine
Authors: Clough D. W. , Wigdahl Brian L. , Parkhurst J. Rodney
Published: June 2012

5-Carboxy-2′-deoxyuridine (5-COOH-2′-dUrd) is a product of the base-catalyzed hydrolysis of 5-trifluoromethyl-2′-deoxyuridine. Hydrolysis of 5-trifluoromethyl-2′-deoxyuridine to 5-COOH-2′-dUrd in phosphate-buffered saline was kinetically first order and was pH dependent. At 37°C and pH 7.0, 7.5, and 8.0, hydrolysis occurred with rate constants of 4.19 × 10
−5
, 9.30 × 10
−5
, and 1.61 × 10
−4
s
−1
, respectively, with corresponding half-lives of 45.7, 20.6, and 11.9 h. 5-COOH-2′-dUrd inhibited growth of HEp-2 cells by 21, 67, and 91% at 1.0, 10, and 100 μM, with no antiviral activity against herpes simplex virus type 1 or herpes simplex virus type 2 at 1.0 or 10 μM. Partial reversal of cytotoxicity in HEp-2 cells was achieved with orotidine, uridine, deoxythymidine, or deoxycytidine, whereas complete reversal of cytotoxic effects was achieved with simultaneous addition of deoxythymidine, deoxycytidine, and uridine. 5-COOH-2′-dUrd at 50 μM inhibited incorporation of [
14
C]orotate into RNA and DNA by 65 and 27%, respectively. 5-COOH-2′-dUrd had no effect on the incorporation of [
3
H]uridine into DNA or RNA. Because of the structural similarities to deoxythymidine, 5-COOH-2′-dUrd was tested as an inhibitor of deoxythymidine kinase. 5-COOH-2′-dUrd was neither a substrate nor an inhibitor of herpes simplex virus type 1 induced deoxythymidine kinase or HEp-2 cell deoxythymidine kinase. Based on these observations, the metabolic block induced by 5-COOH-2′-dUrd has been localized to the de novo pyrimidine biosynthetic pathway between orotate phosphoribosyl transferase and orotidine 5′-phosphate decarboxylase.
Double-Blind Comparison of Cefamandole and Penicillin in Pneumococcal Pneumonia
Authors: Petty Brent G. , Smith Craig R. , Wade James C. , Conrad Gary L. , Lipsky James J. , Ellner Jerrold J. , Lietman Paul S.
Published: June 2012

We conducted a prospective, randomized, double-blind comparison of intravenous penicillin and cefamandole in the therapy of pneumococcal pneumonia. Patients received either 1 g of cefamandole or 600,000 U of aqueous penicillin G every 6 h. Of the 100 patients entered into the study, 96 had clinical and radiographic evidence of pneumonia. Microbial etiology was determined from the results of sputum and blood cultures and/or sputum Gram stains.
Streptococcus pneumoniae
was pathogenic in 49 patients, of whom 24 received cefamandole and 25 received penicillin. There was no statistically significant difference in the response or cure rate. Of the 100 patients, 93 were treated for 3 days or more and were evaluated for adverse effects and toxicity. There was no significant difference between cefamandole-treated and pencillin-treated patients in the incidence of colonization, superinfection, phlebitis, thrombocytosis, decrease in hematocrit, or elevated liver function tests. Eosinophilia occurred more frequently in patients treated with penicillin (20 of 42) than in those treated with cefamandole (11 of 42 (chi square,
P
< 0.05). Only one patient receiving cefamandole developed a positive direct Coombs test. No patient in either group developed meningitis. We conclude that, with the doses and route of administration employed in this study, cefamandole is as effective as penicillin in the therapy of pneumococcal pneumonia without an increased incidence of colonization, superinfection, or adverse effects.
Effect of Leaf Extracts of
Aloe arborescens
Mill subsp.
natalensis
Berger on Growth of
Trichophyton mentagrophytes
Authors: Fujita Keisuke , Yamada Yasuo , Azuma Keizou , Hirozawa Susumu
Published: June 2012

The antifungal activity of a lyophilized powder containing aloe leaf homogenate (whole-leaf powder) against
Trichophyton mentagrophytes
was investigated. The minimal inhibitory concentration was 25 mg/ml by the agar dilution method, using Sabouraud glucose agar medium. At subinhibitory concentrations, the powder exerted its main effect on colony growth by prolongation of the lag phase and inhibition of growth rate. Homogenates of fresh whole leaf were filtered through Whatman GF/A paper, and the filtrate was dialyzed and concentrated by molecular filtration using an Amicon hollow-fiber dialyzer concentrator DC-2, and a powder containing components with molecular weights higher than 10,000 (high-molecular-weight component powder) was prepared by lyophilization. The minimal inhibitory concentrations against three strains of
T. mentagrophytes
were all 10 mg/ml. The inhibitory activity was fungicidal and was lost by heating at 100°C for 30 min. Both the whole-leaf powder and the high-molecular-weight component powder induced various morphological abnormalities in spores and hyphae by the inhibition of spore germination and development of hyphae.
Comparative In Vivo Activities of Cefsulodin, Sulbenicillin, and Gentamicin Against
Pseudomonas aeruginosa
Authors: Kondo Masahiro , Tsuchiya Kanji
Published: June 2012

The in vivo activities of cefsulodin, sulbenicillin, and gentamicin were compared in mice infected intraperitoneally with
Pseudomonas aeruginosa
. In mice infected with sulbenicillin- and gentamicin-susceptible strains, cefsulodin was about 12 to 60 times more active than sulbenicillin and had an activity similar to gentamicin. In mice, the activity of cefsulodin was independent whether the strains were resistant to gentamicin or not, but it was considerably affected by resistance of the strains to sulbenicillin.
Transferable Chloramphenicol and Ampicillin Resistance in a Strain of
Haemophilus influenzae
Authors: Bryan L. E.
Published: June 2012

A strain of
Haemophilus influenzae
isolated from sputum has been shown to be resistant to chloramphenicol, ampicillin, and tetracycline. All three resistances were transferred together to recipients when the selecting antibiotic was ampicillin, chloramphenicol, or tetracycline.
Streptococcin A-FF22: Nisin-Like Antibiotic Substance Produced by a Group A Streptococcus
Authors: Tagg J. R. , Wannamaker L. W.
Published: June 2012

Streptococcin A-FF22 (SA) was shown to occur as both a cell-associated (SA-CA) and an extracellular (SA-EX) component of cultures of the producer bacterium, group A streptococcus strain FF22. SA-CA was solubilized by chemical, enzymatic, and mechanical procedures, similar to those used to release M protein. The independence of SA and M protein in strain FF22 was established by chromatographic separation of the two proteins on the basis of molecular weight and isoelectric point differences between the two substances. Media supporting optimal growth of strain FF22 did not necessarily favor SA production. SA was not produced either at elevated temperatures (39°C) or if the culture was maintained at pH 7 or higher. The release of SA from producer cells was enhanced at lower culture pH values. Much of the SA-CA activity seemed associated with the cell walls of the producer strain, and the nature of the binding appeared to be largely nonspecific in nature and attributable to electrostatic interaction.
Enzymatic Modification of Aminoglycoside Antibiotics: 3-
N
-Acetyltransferase with Broad Specificity that Determines Resistance to the Novel Aminoglycoside Apramycin
Authors: Davies Julian , O'Connor Sean
Published: June 2012

Examination of a number of R-plasmid-containing bacterial isolates of animal origin has revealed the presence of a new aminoglycoside acetyltransferase (3-
N
) with a broad substrate range that includes all the disubstituted 2-deoxystreptamine antibiotics and also the novel monosubstituted antibiotic apramycin. Antibiotic derivatives acylated with hydroxyaminobutyric acid at the 1-amino position were not modified by the enzyme.
Combined Activity of Clavulanic Acid and Ticarcillin Against Ticarcillin-Resistant, Gram-Negative Bacilli
Authors: Paisley John W. , Washington John A.
Published: June 2012

Fifty-one clinical isolates of ticarcillin-resistant, gram-negative bacilli were tested for susceptibility to combinations of ticarcillin and clavulanic acid (BRL 14151), a potent beta-lactamase inhibitor. Minimal inhibitory concentrations (MICs) were measured by a microdilution method, and minimal bactericidal concentrations for selected strains were measured by the broth dilution method. Ticarcillin MICs were ≥128 μg/ml for all and ≥512 μg/ml for 38 (75%) of the strains. Thirty-nine strains of
Enterobacteriaceae
tested included
Escherichia coli
(14),
Klebsiella pneumoniae
(16),
Citrobacter
sp. (3),
Enterobacter
sp. (3),
Salmonella enteritidis
(1),
Serratia marcescens
(1), and
Proteus mirabilis
(1). Ticarcillin MICs for 34 strains (88%) were lowered at least threefold by the addition of 1.0 μg of clavulanic acid per ml. Against 33 strains (85%), the MICs were 64 μg or less per ml in the presence of 5 μg of clavulanic acid per ml. In contrast, the MICs for seven of eight strains of
Pseudomonas aeruginosa
were unaffected by the addition of up to 10 μg of clavulanic acid per ml. Ticarcillin with 5 μg of clavulanic acid per ml was bactericidal against ticarcillin-resistant (MIC ≥ 2,048 μg/ml)
E. coli, K. pneumoniae, Enterobacter
, and
P. mirabilis
.
Ascitic Fluid Cephalosporin Concentrations: Influence of Protein Binding and Serum Pharmacokinetics
Authors: Gerding Dale N. , Peterson Lance R. , Legler Dwight C. , Hall Wendell H. , Schierl Elizabeth A.
Published: June 2012

Mongrel dogs with ascites created by inferior vena cava ligation were given cephalothin, cephaloridine, cefazolin, and cefamandole to evaluate the effect of protein binding and serum pharmacokinetics on the distribution of cephalosporins into ascitic fluid. Antibiotics were given intramuscularly (15 mg/kg) every 4 h for a total of eight doses. Antibiotic binding to dog serum and ascitic fluid was measured by ultracentrifugation. Binding of the cephalosporins to dog serum ranged from 31% for cephaloridine to 46% for cephalothin, considerably lower than human serum binding for cefazolin, cephalothin, and cefamandole. Antibiotic binding to ascitic fluid was only slightly lower than that to serum. Ascitic fluid antibiotic concentrations, which approached equilibrium at 16 to 28 h, were significantly higher for cefazolin and cephaloridine than for cephalothin and cefamandole. However, serum concentrations were also higher for cefazolin and cephaloridine, and percent penetration (ratio of serum peak to ascites peak × 100) was not statistically different among the four drugs. Binding of these cephalosporins to extravascular fluid protein was an important factor that determined the total ascitic fluid antibiotic level achieved. A formula utilizing the log mean serum level and binding to serum and extravascular fluid protein was used to accurately predict ascitic fluid drug levels at equilibrium.
Effect of Low Concentrations of Dihydrostreptomycin on Drug Resistance in Enteric Bacteria
Authors: Gaines S. A. , Rollins L. D. , Silver R. P. , Washington M.
Published: June 2012

Beagle dogs were fed a diet containing 0, 2, or 10 μg of dihydrostreptomycin (DSM) per g of feed. The 2-μg/g level was selected to represent a residue level of the antibiotic. In both treatment groups, medicated feed resulted in a shift from a predominantly streptomycin (SM)-susceptible coliform fecal population to an SM-resistant population. The proportion of resistant organisms was significant (
P
< 0.01) for both treatment groups. A definitive response did not occur with animals maintained on DSM-free diets. An increase in the prevalence of DSM-resistant organisms was observed after 15 days of DSM-supplemented feeding and persisted during the posttreatment phase of the study. The predominant pattern of resistance was SM-sulfamethoxypyridazine. Fifty-nine percent of SM-resistant strains transferred resistant determinants by conjugation to
Escherichia coli
K-12 recipients.
Susceptibility of Anaerobic Bacteria to Ten Antimicrobial Agents
Authors: Appelbaum Peter C. , Chatterton Sheila A.
Published: June 2012

The susceptibility pattern of 265 anaerobic bacteria from clinical isolates to 10 antimicrobial agents was investigated by the agar dilution technique. Penicillin G, in a concentration of 16 μg/ml, was active against most organisms, important exceptions being 12% of
Bacteroides melaninogenicus
and 24% of
B. fragilis
strains. The susceptibility of strains to ampicillin was similar to their susceptibility to penicillin G. Carbenicillin, at ≤128 μg/ml, inhibited all but a few strains. Cefamandole was less active than the penicillins; 82% of
B. melaninogenicus
, 32% of
B. fragilis
, and 75% of
Fusobacterium
strains were inhibited by ≤16 μg/ml. A trend towards tetracycline resistance was seen in many bacterial groups, especially
Bacteroides, Fusobacterium
, and
Clostridium
. All organisms were susceptible to chloramphenicol and clindamycin in concentrations of ≤16 μg/ml and ≤4 μg/ml, respectively. Erythromycin was less active than clindamycin against all strains tested. Metronidazole and tinidazole were active against most anaerobes, but resistance of a few strains in each group was encountered. The increased resistance of
B. melaninogenicus
strains to penicillin, and emergence of anaerobes resistant to >16 μg of imidazole per ml may have therapeutic implications.
In Vitro Activity of 5-Episisomicin in Bacteria Resistant to Other Aminoglycoside Antibiotics
Authors: Kabins Sherwin A. , Nathan Catherine
Published: June 2012

Eighty-seven isolates of
Pseudomonas, Enterobacteriaceae
, and
Staphylococcus
, chosen because of their resistance to other aminoglycosides, were tested for susceptibility to 5-episisomicin. Tests were performed in Mueller-Hinton agar and also, with 38 of these isolates, in Mueller-Hinton broth. Of
Enterobacteriaceae
, 85 and 95.5% were inhibited by 5 and 10 μg of 5-episisomicin per ml, respectively. Amikacin inhibited 74 and 91% of the strains at 10 and 20 μg/ml, respectively. Fifty-four percent of
P. aeruginosa
were inhibited by 5-episisomicin and amikacin. Eighty-three percent of
S. aureus
were inhibited by netilmicin and amikacin, whereas only 50% were inhibited by 5-episisomicin. Isolates resistant to 5-episisomicin were most often resistant to the other aminoglycosides and occurred in gram-negative bacilli that did not carry aminoglycoside-modifying enzymes. Five of 23 isolates that carried a 6′-
N
-acetyltransferase (AAC-6′) and one of two that carried an aminoglycoside 3-acetyltransferase were resistant to and acetylate 5-episisomicin. Strains carrying other aminoglycoside-modifying enzymes were inhibited by 5-episisomicin. Thus, 5-episisomicin is a promising aminoglycoside not attacked by most aminoglycoside-modifying enzymes. Resistance will probably most often be based upon nonenzymatic mechanisms which will also affect other aminoglycosides.
High-Performance Liquid Chromatographic Assay of Chloramphenicol in Serum
Authors: Koup Jeffrey R. , Brodsky Barbara , Lau Alan , Beam Thomas R.
Published: June 2012

A new method for the analysis of serum chloramphenicol by reversed-phase, high-performance liquid chromatography (HPLC) is described. The method involves a preliminary extraction of 0.1 ml of serum with ethyl acetate containing an internal standard, chromatography with a reversed-phase C18 microparticulate column with an acetonitrile-acetate buffer mobile phase, and detection by measuring UV absorbance at 270 nm. Assay performance was compared with an existing microbiological assay. The HPLC method demonstrated both increased precision and increased sensitivity. The specificity of the HPLC method was also evaluated. The new method presents an alternative approach to the analysis of clinical specimens.
Pharmacological Evaluation of Cefaclor in Volunteers
Authors: Hodges Glenn R. , Liu Chien , Hinthorn Daniel R. , Harms Jane L. , Dworzack David L.
Published: June 2012

The plasma and urine concentrations of cefaclor were measured after oral administration of single and multiple doses to volunteers. Cefaclor was rapidly absorbed, rapidly excreted in the urine, well tolerated without toxicity, and failed to accumulate in the plasma with chronic dosing.
Effect of Hadacidin on Growth and Adenylosuccinate Synthetase Activity of
Dictyostelium discoideum
Authors: Rossomando Edward F. , Maldonado Barbara , Crean Edmund V.
Published: June 2012

The growth of the eucaryotic microorganism
Dictyostelium discoideum
in liquid culture was completely inhibited by the aspartic acid analog hadacidin (
N
-formylhydroxyamino-acetic acid). Growth arrest occurred both in chemically defined medium and in complex growth medium containing aspartic acid and AMP precursors such as adenine and adenosine. Although these compounds could not overcome the effect of hadacidin, growth was restored if cells were washed and resuspended in fresh growth medium. Additional experiments showed that
D. discoideum
contains adenylosuccinate synthetase, the enzyme which catalyzes the synthesis of adenylosuccinate from IMP, aspartic acid, and GTP in the de novo biosynthesis of purines. A partially purified preparation of this enzyme was obtained, and the effect of hadacidin on its activity was studied. We found that maximum inhibition of the
D. discoideum
activity occurs at a ratio of aspartic acid to hadacidin of 5:1, suggesting that the affinity of the drug for this enzyme is less than for the enzyme from rabbit muscle and plants but greater than for that from
Escherichia coli
. The effect of the drug can be overcome by a 10-fold excess of aspartic acid, suggesting that the drug acts as a competitive inhibitor. A comparison of the adenylosuccinate synthetase activity levels at various stages of growth showed that its specific activity decreases about 60% as cells enter the stationary growth phase, and decreases about 75% after starvation for 2 h. Further studies showed that in cells treated with hadacidin the rate of uptake of exogenous nutrients is reduced about 75% and that these cells are more resistant to rupture by osmotic shock. While the results of this study are consistent with the proposal that growth arrest is contingent upon inhibition of adenylosuccinate synthetase activity, they also suggest that, as a consequence of this inhibition, some physiological properties of the cell have been altered.
Antimicrobial Susceptibility of Flavobacteria
Authors: Aber Robert C. , Wennersten Christine , Moellering Robert C.
Published: June 2012

Antimicrobial susceptibility patterns of 28 clinical isolates of
Flavobacterium
sp. were determined by standard disk diffusion technique and by antimicrobial dilution in agar. Rifampin, clindamycin, trimethoprim-sulfamethoxazole, cefoxitin, and vancomycin are among the antimicrobial agents which may be clinically useful to treat infections caused by flavobacteria. All 28 isolates were resistant to erythromycin with minimal inhibitory concentrations of 32 μg/ml or more. Currently recommended interpretive zones of inhibition by disk diffusion did not reliably predict antimicrobial susceptibility of the 28 flavobacteria isolates when compared with the agar dilution technique, and, therefore, a more direct measurement of minimal inhibitory or bactericidal concentration is recommended.
Disk Agar Diffusion Susceptibility Testing of Yeasts
Authors: Saubolle Michael A. , Hoeprich Paul D.
Published: June 2012

A disk agar diffusion method was developed for testing the susceptibility of rapidly growing yeasts in vitro. A totally defined, completely synthetic agar culture medium (synthetic amino acid medium, fungal) and clinical isolates of
Candida
spp. and
Torulopsis glabrata
were used. Turbidimetric adjustment of cell suspensions resulted in standard, reproducible inocula, which gave sharp, clear zones of inhibition when applied by an agar overlay method. Optimal disk loads were determined for amphotericin B, amphotericin B methyl ester, 5-fluorocytosine, clotrimazole, and miconazole. Disk potencies were stable over a 2-month period when stored in a vacuum desiccator at −30°C. Using an error ratebounded classification, the zones of inhibition were correlated with both broth dilution and agar dilution minimum inhibitory concentrations (MICs). With amphotericin B and amphotericin B methyl ester, all isolates were susceptible, yielding zone diameters which clustered within 5 mm. Overall correlations between zone diameters and broth dilution MICs with 5-fluorocytosine, miconazole, and clotrimazole were 97, 96, and 82% (excluding
T. glabrata
), respectively; correlations of zone diameters with agar dilution MICs were 96, 92, and 88%, respectively. Disk diffusion susceptibility testing of yeasts appears to be generally applicable. However, when results are equivocal, quantitative test methods should be used.
Effects of Binding and Bactericidal Action of Vancomycin on
Bacillus licheniformis
Cell Wall Organization as Probed by
15
N Nuclear Magnetic Resonance Spectroscopy
Authors: Irving Charles S. , Lapidot Aviva
Published: June 2012

The effects of binding and the bactericidal action of vancomycin on the arrangement and mobilities of cell wall polymers in
Bacillus licheniformis
were investigated by
15
N nuclear magnetic resonance spectroscopy. The bactericidal action of vancomycin led to reduced mobilities of cell wall teichoic acid and teichuronic acid in surviving cells. The decrease in teichoic acid mobility was also observed upon binding of vancomycin to
B. licheniformis
cells and resulted from a specific interaction between the antibiotic and teichoic acid, rather than from electrostatic contraction of the cell wall. The reduction in teichuronic acid mobility appeared to be related either to the elastic contraction of the cell wall resulting from loss of cell turgor or to separation of the cell wall from the protoplast membrane. No spectral changes associated with cell wall autolysis or alterations in cell wall composition, amidation, and cross-linking were found in vancomycin-treated
B. licheniformis
cells. Binding of vancomycin to
Micrococcus lysodeikticus
cell walls led to a decrease in mobility of C-terminal
d
-alanine residues but was accompanied by an increase in the mobilities of other peptidoglycan residues. The possible contributions of changes in the arrangements of cell wall polymers to the lethal action of vancomycin is discussed.
Effect of Treatment with 5-Ethyl-2′-Deoxyuridine on Herpes Simplex Virus Encephalitis in Normal and Immunosuppressed Mice
Authors: Davis William B. , Oakes John E. , Taylor John A.
Published: June 2012

5-Ethyl-2′-deoxyuridine (5-ethyl-dUrd), an analog of thymidine, was evaluated for its capacity to inhibit herpes simplex virus (HSV) replication in vitro and in vivo. The 50% effective dose concentration of 5-ethyl-dUrd for HSV types 1 and 2 (HSV-1 and -2) cultured in Vero cells was 6 and 9 μg/ml, respectively. Levels of 5-ethyl-dUrd 14-fold in excess of the 50% effective dose for HSV-1 did not inhibit the formation of confluent monolayers by Vero cells, suggesting that the compound was not cytotoxic or inhibitory for mammalian cells. In vivo studies showed that 5-ethyl-dUrd was effective in significantly reducing mortality when administered to young adult mice after subcutaneous infection with HSV-2. Intraperitoneal and intravenous inoculation of drug (250 mg/kg per day) resulted in a 50% survivor rate at 15 days. Comparative studies with adenine arabinoside at 250 mg/kg per day gave a 40% survivor rate. Intramuscular injection of 5-ethyl-dUrd at a concentration as high as 2,000 mg/kg per day for 10 days was well tolerated by uninfected animals, and HSV-2-infected mice treated at this dosage had a 100% survival rate. Treatment with 5-ethyl-dUrd at a concentration of 500 mg/kg per day significantly increased the mean survival times of HSV-1- and HSV-2-infected mice immunosuppressed by irradiation; however, the fatal course of the infection was not altered. Assay for virus in tissues showed that 5-ethyl-dUrd treatment delayed progression of the infection into the central nervous system, indicating suppression of virus replication in the tissues.
Characterization of a Bacteriocinogenic Plasmid in
Clostridium perfringens
CW55
Authors: Mihelc Valerie A. , Duncan Charles L. , Chambliss Glenn H.
Published: June 2012

A bacteriocinogenic strain of
Clostridium perfringens
was exposed to various curing agents known to accelerate the elimination of extrachromosomal DNA, and 20 independently derived mutants that had lost both the ability to produce bacteriocin and their immunity to it were isolated and characterized. All of the mutants were missing at least two specific plasmid bands seen in the agarose gel plasmid profile of the parent strain. Evidence that the two missing bands represented the open circular and closed circular forms of the same plasmid was obtained by X-ray nicking and restriction endonuclease digestion. The data indicated that bacteriocin production and immunity are controlled by a single plasmid, pCW4, with a molecular weight of 5.6 × 10
6
in this strain. Attempts to transfer the bacteriocinogenic plasmid were unsuccessful.
Pharmacokinetics of Mezlocillin in Healthy Volunteers
Authors: Bergan Tom
Published: June 2012

Mezlocillin in doses of 1.0, 2.0, and 5.0 g and carbenicillin in doses of 2.0 g were given as bolus injections intravenously to 10 healthy volunteers. For mezlocillin, dose-dependent pharmacokinetics was detected. This is reflected by a more than proportional rise in serum concentrations and a decreased total body clearance as doses were increased. Per dose unit, the areas under serum concentration curves to infinity were 33.5 μg·h/ml for the 1.0-g dose, 47.2 μg·h/ml for the 2.0-g dose, and 54.8 μg·h/ml for the 5.0-g dose. The body clearance fell from 31.2 liters/h with the 1.0-g dose to 17.0 liters/h with the 5.0-g dose. This can be explained mainly by a marked depression of nonrenal clearance, which fell from 12.2 to 3.8 liters/h, compared with a parallel change in renal clearance from 19.0 to 13.2 liters/h. Contributing to the non-linearity may be biotransformation, evacuation via bile, or another process. With dose increments, rising amounts are recovered unchanged in the urine—61% after a 1.0-g dose compared with 69% after a 5.0-g dose. This clearly defines metabolism as a major factor of elimination. Carbenicillin, for which the first-order, two-compartment open model was applicable here as in previous studies, had a longer serum half-life than did mezlocillin. For the 2.0-g doses, the former had a half-life of 1.4 h, compared with 0.8 h for the latter (calculated as if the two-compartment model were fully valid). The relative area under the curve (see above) was 76.1 μg·h/ml after the 2.0-g dose.
Cation Transport Alteration Associated with Plasmid-Determined Resistance to Cadmium in
Staphylococcus aureus
Authors: Weiss Alison A. , Silver Simon , Kinscherf T. G.
Published: June 2012

Plasmid-determined resistance to cadmium has only been found with plasmids from
Staphylococcus aureus
. Resistance to cadmium was associated with a lower accumulation of Cd
2+
ions by the plasmid-bearing resistant cells. Cadmium accumulation by susceptible cells was energy dependent and had those characteristics usually associated with a transmembrane active transport system. There was a specific interrelationship between cadmium accumulation and manganese accumulation and retention. Cd
2+
inhibited the uptake of Mn
2+
and accelerated the loss of intracellular Mn
2+
by the susceptible cells, but was without effect on Mn
2+
transport in resistant
S. aureus
cells. Under similar conditions, there was no differential effect of Cd
2+
on Mg
2+
, Zn
2+
, Co
2+
, Ni
2+
, or Rb
+
accumulation or exchange between the susceptible and the resistant strains.
Evidence for Conversion of 5-Fluorocytosine to 5-Fluorouracil in Humans: Possible Factor in 5-Fluorocytosine Clinical Toxicity
Authors: Diasio Robert B. , Lakings Duane E. , Bennett John E.
Published: June 2012

A gas chromatographic-mass spectrometric method for detecting 5-fluorouracil (5-FU) in serum at concentrations as low as 10 ng/ml was used to determine to what extent 5-FU was present in the serum of patients taking oral 5-fluorocytosine (5-FC). Preliminary studies in two patients and two healthy volunteers given an initial 2-g oral dose of 5-FC demonstrated sustained serum 5-FU levels (>100 ng/ml) during the 5 h after ingestion of drug. Pharmaceutical preparations of 5-FC used in these studies were shown to be insignificantly contaminated with 5-FU (<0.03%), suggesting in vivo conversion of 5-FC to 5-FU had occurred. Serum samples from seven patients with cryptococcal meningitis treated with amphotericin B and 5-FC were examined for 5-FU. Five of these patients had experienced hematological or other toxicity attributed to 5-FC at some time during the course of therapy. Of 41 serum samples, 20 were observed to have 5-FU levels greater than 1,000 ng/ml in the range observed with cancer chemotherapeutic doses of 5-FU known to be associated with hematological toxicity. It is concluded that conversion of 5-FC to 5-FU occurs in humans and furthermore that 5-FU may account for some of the toxicity observed with 5-FC.
Polymyxin B-Penicillin Antagonism in
Proteus Mirabilis
Authors: Sud Inder Jit , Feingold David S.
Published: June 2012

Polymyxin B protects
Proteus mirabilis
from usually lethal penicillin concentrations.
Inappropriate Antidiuretic Hormone Following Adenine Arabinoside Administration
Authors: Ramos E. , Timmons R. F. , Schimpff S. C.
Published: June 2012

A patient with disseminated herpes zoster developed a syndrome of inappropriate antidiuretic hormone and profound hyponatremia secondary to the administration of adenine arabinoside.
Pharmacokinetics of Amoxicillin: Dosage Nomogram for Patients with Impaired Renal Function
Authors: Humbert Guy , Spyker Daniel A. , Fillastre J. P. , Leroy Annie
Published: June 2012

Amoxicillin pharmacokinetics after intravenous administration were studied in patients with normal renal function, with impaired renal function, and during hemodialysis. The average urinary recovery was 68% in patients with normal renal function. Serum half-life was highly correlated (r = 0.967) with creatinine clearance corrected for body weight. Expected half-life was 71 min for a corrected creatinine clearance of 100 ml/min per 70 kg and 16 h in the anephric patient. Average amoxicillin half-life on hemodialysis was 3.6 h. We present a dosage nomogram for making appropriate adjustments to loading dose based on patient weight and maintenance dose based on corrected creatinine clearance.
Methicillin Potentiates the Effect of Gentamicin on Methicillin-Resistant
Staphylococcus aureus
Authors: Hemmer Robert J. P. , Vaudaux Pierre , Waldvogel Francis A.
Published: June 2012

Methicillin-resistant
Staphylococcus aureus
(MRSA) strains show an unusual type of resistance at 37°C; only a small subpopulation of cells is resistant to the β-lactam antibiotics. Incubation in the presence of methicillin (MET), however, results in the emergence of a homogenous population highly resistant to MET. The purpose of the present study was to determine whether MET, despite its lack of killing effect on MRSA, would promote the bactericidal effect of gentamicin (GM), as demonstrated for MET-susceptible strains of
S. aureus
. Eleven epidemiologically distinct strains of MRSA were incubated with MET at various concentrations, in the presence or absence of sub-bactericidal concentrations (1/5 or 1/10 of the minimal bactericidal concentration) of GM, and tested for the synergistic action of both antibiotics by three different methods. Population analysis of the 11 strains in the presence of high concentrations of MET showed that the addition of GM at 1/5 or 1/10 of its minimal bactericidal concentration resulted in marked killing of the 11 strains. Time-kill curves obtained with 32 μg of MET per ml and GM at 1/5 or 1/10 of its minimal bactericidal concentration confirmed this synergistic killing at 24 h. These results were further documented by the checkerboard method on two strains. We conclude that the synergism between MET and GM, previously demonstrated for MET-susceptible
S. aureus
, holds true for MRSA as well and that it can be demonstrated at sub-bactericidal concentrations of GM.
Pharmacology of Cinoxacin in Humans
Authors: Black Henry R. , Israel Karen S. , Wolen Robert L. , Brier Gordon L. , Obermeyer Boyd D. , Ziege Edgar A. , Wolny James D.
Published: June 2012

Cinoxacin was almost completely absorbed when given orally and was found to be approximately 60 to 70% protein bound. Peak serum concentrations were reached within 2 h, and detectable serum concentrations persisted up to 12 h after administration of 0.25-, 0.5-, and 1-g multiple oral doses. Although food delayed the absorption and caused a 30% reduction in mean peak serum concentrations, the overall 24-h urinary recovery was not significantly altered. Approximately 50 to 55% of the drug was excreted in the urine as unchanged drug. At 12 h, urine concentrations were still above the minimal inhibitory concentration for most common gram-negative urinary pathogens. Cinoxacin was well tolerated when administered to 23 volunteers from 10 to 28 days. Resistance among fecal isolates initially susceptible to cinoxacin was not observed in nine volunteers who were administered 0.5 g every 12 h for 4 to 28 days.
Clindamycin in Treatment of Aspiration Pneumonia in Children
Authors: Brook Itzhak
Published: June 2012

Twenty-eight patients with anaerobic pleuropulmonary infections were treated with clindamycin alone or clindamycin with gentamicin. Sixteen of the patients presented with pneumonitis, nine with necrotizing pneumonia, and three with lung abscesses. The average length of treatment was 13.8 days, and the duration of temperature after initiation of therapy was 3.1 days. The predominant isolates were anaerobic gram-positive cocci (23 isolates),
Bacteroides melaninogenicus
(14),
Bacteroides fragilis
(9), and
Fusobacterium nucleatum
(11). The most frequent aerobic isolates were alpha-hemolytic streptococci (12),
Diplococcus pneumoniae
(12),
Pseudomonas aeruginosa
(9),
Klebsiella pneumoniae
(7), group A beta-hemolytic streptococci (5),
Staphylococcus aureus
(9), and
Escherichia coli
(6). All patients responded to the therapy and were cured of the infection. There were no side effects observed from the administration of clindamycin. None of the patients developed any blood dyscrasia, liver damage, diarrhea, or colitis. Clindamycin appears to be effective in the treatment of mixed aerobic and anaerobic pleuropulmonary infections in children, alone or with an aminoglycoside when indicated.
Comparison of Anaerobic Susceptibility Results Obtained by Different Methods
Authors: Rosenblatt J. E. , Murray P. R. , Sonnenwirth A. C. , Joyce J. L.
Published: June 2012

Susceptibility tests using 7 antimicrobial agents (carbenicillin, chloramphenicol, clindamycin, penicillin, cephalothin, metronidazole, and tetracycline) were run against 35 anaerobes including
Bacteroides fragilis
(17), other gram-negative bacilli (7), clostridia (5), peptococci (4), and eubacteria (2). Results in triplicate obtained by the microbroth dilution method and the aerobic modification of the broth disk method were compared with those obtained with an agar dilution method using Wilkins-Chalgren agar. Media used in the microbroth dilution method included Wilkins-Chalgren broth, brain heart infusion broth, brucella broth, tryptic soy broth, thioglycolate broth, and Schaedler's broth. A result differing by more than one dilution from the Wilkins-Chalgren agar result was considered a discrepancy, and when there was a change in susceptibility status this was termed a significant discrepancy. The microbroth dilution method using Wilkins-Chalgren broth and thioglycolate broth produced the fewest total discrepancies (22 and 24, respectively), and Wilkins-Chalgren broth, thioglycolate, and Schaedler's broth had the fewest significant discrepancies (6, 5, and 5, respectively). With the broth disk method, there were 15 significant discrepancies, although half of these were with tetracycline, which was the antimicrobial agent associated with the highest number of significant discrepancies (33), considering all of the test methods and media.
Avermectins, New Family of Potent Anthelmintic Agents: Isolation and Chromatographic Properties
Authors: Miller Thomas W. , Chaiet Louis , Cole Douglas J. , Cole Lucille J. , Flor James E. , Goegelman Robert T. , Gullo Vincent P. , Joshua Henry , Kempf August J. , Krellwitz Wilson R. , Monaghan Richard L. , Ormond Robert E. , Wilson Kenneth E. , Albers-Schönberg George , Putter Irving
Published: June 2012

The avermectins, a family of new anthelmintic agents, were isolated from the mycelia of
Streptomyces avermitilis
. Four closely related major components and four homologous minor components were separated from the complex. Solvent extraction, solvent partition, and adsorption methods were used to isolate and purify the complex; novel partition chromatography systems using Sephadex LH-20 were used to separate the components. A reverse-phase high-pressure liquid chromatography assay for the quantitative determination of all components was used extensively to monitor the purification methods.
In Vitro Activity of 39 Antimicrobial Agents Against
Treponema hyodysenteriae
Authors: Kitai Kazuhisa , Kashiwazaki Mamoru , Adachi Yoshikazu , Kume Tsuneo , Arakawa Akira
Published: June 2012

The in vitro activities of 39 antimicrobial agents against 23 isolates of
Treponema hyodysenteriae
, the majority of which were field isolates, were determined by the agar dilution technique. Quinoxalines, pleuromutilin, nitroimidazoles, and nitrofuran were the most active. Their activities ranged from ≤0.10 to 1.56 μg/ml. Lincomycin, penicillins, chloramphenicol, tetracyclines, cephalosporins, three peptides (virginiamycin, thiopeptin, and bacitracin), and one aminoglycoside (gentamicin) exhibited intermediate levels of activity ranging from 0.39 to 50 μg/ml. Four peptides (enduracidin, viomycin, bicyclomycin, and colistin), three aminoglycosides (kanamycin, streptomycin, and neomycin), polyene, and other agents, including novobiocin, vancomycin, rifampin, nalidixic acid, and
p
-arsanilic acid, displayed limited activities ranging from 12.5 to ≥100 μg/ml. Macrolides showed varying degrees of activity depending upon isolates.
Influence of Probenecid on Serum Levels and Urinary Excretion of Cinoxacin
Authors: Rodriguez Nair , Madsen Paul O. , Welling Peter G.
Published: June 2012

Serum levels and urinary excretion of cinoxacin were examined in healthy individuals after a two-step intravenous infusion in the presence and absence of probenecid. After dosing cinoxacin alone, steady-state serum levels were approached in 1 h and were maintained for an additional 2 h with a reduced infusion rate. After probenecid pretreatment, serum levels of cinoxacin continued to increase during 3 h of infusion, reaching levels approximately double those obtained with cinoxacin alone. The mean elimination half-life of cinoxacin from serum was increased from 1.3 to 3.5 h in the presence of probenecid, and renal clearance was significantly reduced, with 46% of dosed drug appearing in 7-h urines of probenecid-treated subjects compared with 68% in subjects receiving cinoxacin alone. Probenecid had no apparent influence on cinoxacin distribution in the body but caused a significant decrease in the rate of cinoxacin extrarenal elimination, possibly due to competition for a common metabolic pathway.
High-Pressure Liquid Chromatographic Assay of Chloramphenicol in Biological Fluids
Authors: Sample R. H. Barry , Glick Melvin R. , Kleiman Martin B. , Smith James W. , Oei Tjien O.
Published: June 2012

Chloramphenicol can be assayed by a sensitive and selective high-pressure liquid chromatographic assay technique. The method described is easily adapted to analysis of many other drugs.
Bactericidal Effect of Combinations of Antimicrobial Drugs and Antineoplastic Antibiotics Against
Staphylococcus aureus
Authors: Jacobs John Y. , Michel Jacques , Sacks Theodore
Published: June 2012

Six antineoplastic antibiotics were tested against ten strains of
Staphylococcus aureus
. Four showed bacteriostatic and/or bactericidal activity against each of the ten strains, and two were only bacteriostatic for seven and nine strains, respectively. Using the cellophane transfer technique, combinations of these antineoplastic antibiotics with 16 antibacterial drugs were screened for combined bactericidal activity. Synergism or antagonism was demonstrated in about one-third of the combinations. Checkerboard titrations and killing curves confirmed these findings and indicated that the effective concentrations of the antibacterial agents were similar to those attainable in the serum after therapeutic doses of these drugs. Although the pharmacokinetics of the six antineoplastic antibiotics in humans are not fully known, at least one of them has a peak serum level corresponding to those values at which a bactericidal effect was produced in vitro.
Nosocomial Multiply Resistant
Klebsiella pneumoniae
: Epidemiology of an Outbreak of Apparent Index Case Origin
Authors: Gerding Dale N. , Buxton Alfred E. , Hughes Rita A. , Cleary Paul P. , Arbaczawski Joseph , Stamm Walter E.
Published: June 2012

A nosocomial epidemic of multiply resistant (MR)
Klebsiella pneumoniae
characterized by resistance to gentamicin, tobramycin, kanamycin, cephalothin, chloramphenicol, and ampicillin occurred in a Veterans Administration hospital from 1975 to 1977. A total of 66 infected or colonized patients were observed in a 2-year period; there were 43 urinary tract infections, 13 wound or soft tissue infections, 8 pneumonias, and 6 patients with only asymptomatic stool colonization. Four patients had both pneumonia and a urinary tract infection. There were five secondary bacteremias. The majority of MR
K. pneumoniae
strains were type 30, but types 17, 21, and 23 and nontypable organisms were also recovered. Other gram-negative bacilli with the same antibiotic resistance pattern were isolated from 14 patients. Seven MR
K. pneumoniae
and three resistant
Escherichia coli
isolates were shown to transfer resistance to
E. coli
K-12. MR
K. pneumoniae
-infected patients were seriously ill, had long hospitalization times (mean, 67 days), and were in close geographic proximity to other cases. Compared with controls, cases more frequently had prior antibiotic treatment and urinary catheters, but not respiratory instrumentation, nasogastric tubes, or antacid treatment. The apparent source of the outbreak was traced to an index case who entered the hospital with an MR
K. pneumoniae
urinary tract infection. Asymptomatic gastrointestinal carriage without infection elsewhere was infrequent (1.6% of cultured patients), but 78% of patients with MR
K. pneumoniae
infections at other sites also had the organism in their stools. Hospital antibiotic usage was unchanged before and during the outbreak. The identification of an index case and relative lack of asymptomatic stool carriers are unique features of this plasmid-mediated MR
K. pneumoniae
epidemic. Although this MR
K. pneumoniae
outbreak appeared to be controlled by the use of isolation techniques, a simultaneous increase in gentamicin resistance among other gram-negative organisms was observed.
Growth Inhibition by Acycloguanosine of Herpesviruses Isolated from Human Infections
Authors: Crumpacker Clyde S. , Schnipper Lowell E. , Zaia John A. , Levin Myron J.
Published: June 2012

Inhibition by acycloguanosine (ACG) of plaque formation by harpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus, and cytomegalovirus was studied. Seventeen clinical isolates of HSV-1 were inhibited by ACG at a mean 50% inhibitory dose (ID
50
) of 0.15 ± 0.09 μM. The mean ID
50
for 10 isolates of HSV-2 was 1.62 ± 0.76 μM, and for four isolates of varicella-zoster virus it was 3.75 ± 1.30 μM. The ID
50
's for two cytomegalovirus isolates were 100 and 160 μM, and for four additional isolates of cytomegalovirus no end point (ID
50
) was reached at 200 μM. ACG at a concentration of 200 μM had no effect on deoxyribonucleic acid synthesis in human fibroblast cells and only inhibited thymidine incorporation by Vero cells by one-third. These studies demonstrated the antiviral activity of ACG against clinical isolates of HSV-1, HSV-2, and varicella-zoster virus and the lack of toxicity to monkey or human cells in culture at concentrations which markedly inhibited these viruses. ACG had little effect on cytomegalovirus at concentrations in excess of 100 μM.