bluuebunny/crossref_metadata_2025 huggingface dataset:
Cefoperazone (T-1551), a new semisynthetic cephalosporin: comparison with cephalothin and gentamicin
Authors: Jones R N , Fuchs P C , Barry A L , Gavan T L , Sommers H M , Gerlach E H
Published: June 2012

The in vitro activity of cefoperazone (T-1551) against almost 9,000 recent clinical isolates at six institutions was tested and compared with that of cephalothin and gentamicin. The modal minimum inhibitory concentrations of cefoperazone were 16- and 4-fold less than those of cephalothin and gentamicin, respectively, against 5,503 strains of Enterobacteriaceae. Species normally resistant to cephalothin, such as indole-positive protease and enterobacters, were almost universally susceptible to cefoperazone. Cefoperazone demonstrated activity comparable to gentamicin against Pseudomonas aeruginosa and other pseudomonads.
In vitro antimicrobial activity of cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and other beta-lactam antibiotics against Neisseria gonorrhoeae and Haemophilus influenzae, including beta-lactamase-producing strains
Authors: Baker C N , Thornsberry C , Jones R N
Published: June 2012

Minimum inhibitory concentrations and agar disk diffusion tests were determined on clinical isolates of beta-lactamase-positive and beta-lactamase-negative Neisseria gonorrhoeae and Haemophilus influenzae with the newer beta-lactam antibiotics, cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and piperacillin, and with seven older beta-lactam antibiotics. All the drugs were active against beta-lactamase-negative strains of N. gonorrhoeae and H. influenzae. The drug most active against beta-lactamase-positive N. gonorrhoeae was cefotaxime, followed closely by cefoperazone, moxalactam, piperacillin, and mezlocillin. The drugs most active against beta-lactamase-positive strains of H. influenzae were cefotaxime, moxalactam, cefoperazone, and cefamandole.
Concentrations of various antibiotics in serum and fluids accumulated in diffusion chambers implanted in various sites in rabbits
Authors: Georgopoulos A , Schütze E
Published: June 2012

Diffusion chambers with Millipore membranes were implanted in soft tissue, kidneys, and peritoneal and pleural cavities of rabbits. Single doses of azlocillin, cefazolin, and gentamicin were injected intramuscularly and ampicillin was administered orally 2--5 weeks after implantation. The concentrations of the respective drugs in simultaneously collected samples of fluid from each diffusion chamber were measured and compared with concentrations found at the same time in serum. All chambers were tolerated well, and the method proved to be effective for collecting data on the distribution of drugs throughout the body.
Purification of the viridicin produced by Aerococcus viridans
Authors: Ballester J M , Ballester M , Belaich J P
Published: June 2012

A new bacteriocin produced by Aerococcus viridans was purified. Bacteria grown on liquid medium synthesized a bacteriocin, viridicin, which can be extracted from the cells by treatment with 0.86 M NaCl solution. Viridicin production was not induced by ultraviolet irradiation or by treatment with mitomycin C. The bacteriocin was purified by ultrafiltration, gel filtration, and preparative polyacrylamide disc gel electrophoresis. The molecular weight was between 100,000 and 120,000. The purified viridicin was homogeneous on polyacrylamide gel electrophoresis. The viridicin was composed of protein, carbohydrate, and lipid.
2'-fluoro-5-iodo-aracytosine, a potent and selective anti-herpesvirus agent
Authors: Lopez C , Watanabe K A , Fox J J
Published: June 2012

A newly synthesized pyrimidine analog, 2'-fluoro-5-iodo-aracytosine (FIAC), suppressed by 90% the replication of various strains of herpes simplex virus types 1 and 2 at concentrations of 0.0025 to 0.0126 microM. Cytotoxicity was minimal, as determined by trypan blue dye exclusion with norman Vero, WI-38, and NC-37 cell proliferation; the 50% inhibitory dose was 4 to 10 microM in a 4-day assay. When compared with other antiviral drugs, FIAC was active at much lower concentrations than arabinosylcytosine, iododeoxyuridine, and arabinosyladenine. It was slightly more active against herpes simplex virus type 1 than acycloquanosine and slightly more toxic to normal cells. FIAC was about 8,000 times more active against the replication of wild-type herpes simplex virus type 1 than against a mutant strain lacking the expression of virus-specified thymidine kinase. Since FIAC appears to be preferentially phosphorylated by the viral enzyme, this is probably responsible, at least in part, for the selectivity of its antiviral actions. Although FIAC appears to be an arabinosylcytosine analog, its antiviral activity was not reversed by deoxycytidine. The minimal cytotoxicity exhibited by FIAC for normal cells, however, was reversed by equimolar concentrations of deoxycytidine. Thymidine, which reversed the antiviral activity, was effective only when used in great excess.
Rapid determination of minimum inhibitory concentrations of antimicrobial agents by regression analysis of light scattering data
Authors: McKie J E , Seo J , Arvesen J N
Published: June 2012

A novel, rapid, automated method for determining the minimum inhibitory concentrations of antimicrobial drugs within ranges acceptable for therapeutic application is described and validated in this report. By employing a simple modification of the Autobac photometer currently in use and in optically clear, modified Mueller-Hinton broth, the method utilizes forward light scattering data measured in the presence of two concentrations of the antimicrobial agent to compute the minimum inhibitory concentrations. Empirically derived regression equations which simultaneously use scattering data from two drug concentrations are employed in this computation, rather than simple breakpoint analysis in which the light scattering measured in the presence of each drug concentration is referred to a threshold level. The minimum inhibitory concentrations obtained with this new method were highly reproducible and, as shown by side by side comparisons were in excellent agreement with the minimum inhibitory cencentrations obtained with the International Collaborative Study broth dilution method.
Rapid determination of minimum inhibitory concentrations of antimicrobial agents by the Autobac method: a collaborative study
Authors: Schoenknecht F D , Washington J A , Gavan T L , Thornsberry C
Published: June 2012

Four laboratories collaborated in an evaluation of the Autobac minimum inhibitory concentration (MIC) test system. The MICs of ranges of MICs determined in this system were compared with the MICs obtained with a microtube modification of the International Collaborative Study broth dilution technique. A total of 1,260 strains, mostly recent clinical isolates and including multiresistant strains, were tested by the four laboratories against 10 antibiotics; 9,360 separate MIC determinations were made. There was an overall agreement of approximately 95% between the two methods. Levels of agreement below 80% were obtained with only 4 of the 104 antibiotic-species pairs. In only one of the four major organism groups (staphylococci and penicillin G) was agreement less than 85%. There was a symmetrical distribution of MIC differences between the two methods. Tests with 56 selected strains were performed in each of four laboratories in an inter- and intra-laboratory reproducibility study. Both methods showed a standard deviation (both inter- and intra-laboratory) of one-half of a twofold dilution step. The Autobac method was actually less variable than the reference method and had equivalent reproducibility. This was particularly true when the Autobac system was operated so that the results generated permitted calculations of MICs via regression analysis.
Plaque inhibition assay for drug susceptibility testing of influenza viruses
Authors: Hayden F G , Cote K M , Douglas R G
Published: June 2012

The relative antiviral activities of four drugs against contemporary strains of influenza A and B viruses were determined in Madin-Darby canine kidney cell monolayers with a plaque inhibition assay. This assay proved to be a reliable, rapid method of determining 50% inhibitory concentrations that correlated well with clinically achievable drug levels and the results of clinical trials. Contemporary strains of influenza A viruses (subtypes H1N1, H3N2, HSW1N1) required amantadine hydrochloride and rimantadine hydrochloride 50% inhibitory concentrations in the range of 0.2 to 0.4 microgram/ml, whereas 50% inhibitory concentrations ranged from approximately 50 to 100 micrograms/ml against influenza B viruses. Ribavirin was approximately 10-fold less active than amantadine hydrochloride against influenza A viruses, and the ribavirin 50% inhibitory concentrations against both influenza A and B viruses ranged from 2.6 to 6.8 micrograms/ml. Inosiplex had no antiviral activity in this test system.
Comparison of in vitro activity of GR 20263, a novel cephalosporin derivative, with activities of other beta-lactam compounds
Authors: Wise R , Andrews J M , Bedford K A
Published: June 2012

The in vitro activity of GR 20263, a new cephalosporin, was compared primarily with the activities of moxalactam (LY 127935), cefotaxime, cefoxitin, cefuroxime, and cefazolin against 293 clinical isolates of a variety of gram-positive and -negative bacteria. The minimal inhibitory concentrations of GR 20263 for 90% of group isolates were between 0.06 and 0.5 microgram/ml for the Enterobacteriaceae, Haemophilus influenzae, Neisseria gonorrhoeae, and Lancefield group A beta-hemolytic streptococci; 2 micrograms/ml for Pseudomonas aeruginosa; 16 micrograms/ml for Staphylococcus aureus; and in excess of 128 micrograms/ml for Bacteroides fragilis and Lancefield group D streptococci. In comparison with the other agents, GR 20263 was markedly more active against the Enterobacteriaceae than cefuroxime, cefoxitin, and cefazolin, but marginally less active than moxalactam or cofotaxime. Aganist S. aureus, cefazolin was 16-fold and cefotaxime was 4-fold more active than GR 20263 and moxalactam. GR 20263 was eight-fold more active than cefotaxime and moxalactam against P. aeruginosa.
Mechanism of virucidal activity of retinoids: protein removal from bacteriophage phi 6 envelope
Authors: Reinhardt A , Auperin D , Sands J
Published: June 2012

The mechanism of the potent virucidal activity of retinol (vitamin A) and retinal (vitamin A aldehyde) was investigated for the interaction of these compounds with a model system enveloped virus, bacteriophage phi 6. The retinoids bind to and inactivate phi 6 without causing large-scale disruption of the virion. Inactivated virions have completely lost the ability to adsorb to host bacteria due to the loss of a viral envelope protein necessary for adsorption.
Combined antibacterial activity of amoxicillin with clavulanic acid against ampicillin-resistant strains
Authors: Matsuura M , Nakazawa H , Hashimoto T , Mitsuhashi S
Published: June 2012

Strains of bacteria resistant to beta-lactam antibiotics have been increasing in number and are becoming troublesome in clinical medicine. The in vitro antibacterial activity of amoxicillin combined with clavulanic acid was determined on selected ampicillin-resistant clinical isolates. Synergistic effects were produced by amoxicillin with clavulanic acid against ampicillin-resistant strains of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, and Bacteroides fragilis. Inhibition of the beta-lactamases produced by the ampicillin-resistant strains was confirmed, especially against the penicillinases mediated by the R factor and the cephalosporinases produced by P.vulgaris and B. fragilis. The inhibitory effect of clavulanic acid against beta-lactamases was irreversible because of the high affinity of clavulanic acid to the enzymes.
Principal beta-lactamases responsible for resistance to beta-lactam antibiotics in urinary tract infections
Authors: Simpson I N , Harper P B , O'Callaghan C H
Published: June 2012

Two independent surveys have been conducted to determine the prevalent bacterial species and beta-lactamase types present in clinical populations of gram-negative, ampicillin-resistant isolates. A total of 208 isolates (112 from Nottingham Hospital and 96 from Charing Cross Hospital), all of which had been collected from out-patients suffering from urinary tract infections, were investigated. The incidence of ampicillin-resistant isolates (minimum inhibitory concentrations, 8 micrograms/ml) was 24.1% and 18.8% within the Nottingham and Charing Cross samples, respectively. The surveys gave similar results within the ampicillin-resistant samples. Escherichia coli was the prevalent bacterial species (52.9%), followed by Klebseilla pneumoniae (30.3%). The majority of isolates, at least 54.8% and possibly as high as 74.5%, owed their principal beta-lactamase activity to enzymes mediated by R-plasmids. The most prevalent beta-lactamases were TEM-1 (53.3%), SHV-1 (30.9%), and OXA-1 (11.5%). Positive associations were found between E. coli and TEM-1 or OXA-1 and between K. pneumoniae and SHV-1.
Some chemical and physical characteristics of pantomycin, and antiobiotic isolated from Streptomyces hygroscopicus
Authors: Gurusiddaiah S , Graham S O
Published: June 2012

The production, isolation, and some structural studies of an antifungal, antibacterial, and antiviral substance from cultures of Streptomyces hygroscopicus are described. This material, designated pantomycin, appears to be a polypeptide antibiotic with inclusion of fatty acids and carbohydrate residues. Amino acid analysis of pantomycin acid hydrolysates indicates that it contains threonine, serine, proline, glycine, alanine, valine, alloisoleucine, and an as-yet-unidentified amino acid which appears to be different from types encountered in proteinaceous materials. In addition to the aforementioned compounds, the antibiotic was shown to contain alpha-aminobutyric acid after hydrogenation. Analysis of ether extracts of the hydrolysate mixture indicated the presence of several fatty aicds; myristic, isotridecanoic, lauric, and undecylic acids. The amino and fatty acid composition of pantomycin is similar to the known antibiotic stendomycin. Pantomycin appears to also have at least one carbohydrate-like residue incorporated into its structure. The presence of carbohydrate was indicated by periodic acid-Schiff base staining of electrophoretic patterns as well as positive color formation in the phenol-sulfuric and Molisch tests, but the carbohydrate did not appear to be either a hexose or a pentose. The antibiotic, which appears to be dissociated in alcoholic solution, forms stable aggregates under aqueous conditons.
Interferon induction by and toxicity of polyriboinosinic acid [poly(rI)].polyribocytidylic acid [poly (rC)], mismatched analog poly (rI).poly[r(C12Uracil)n], and poly(rI).poly(rC) L-lysine complexed with carboxymethylcellulose
Authors: Stringfellow D A , Weed S D
Published: June 2012

The ability of polyriboinosionic acid [poly(rI)].polyribocytidylic acid [poly(rC)], mismatched analog poly (rI).poly[r(C12Uracil)n], and poly(rI).poly(rC) complexed with poly L-lysine and carboxymethylcellulose [poly(ICLc)] to induce interferon and the comparative toxicity of each in cats were evaluated. Each induced high levels of circulating interferon, although poly(ICLC) injected intravenously at 1 to 4 mg/kg induced up to 10 times more interferon than the other compounds. Each compound was pyrogenic and caused a transient decrease in leukocyte numbers. Poly(rI).poly(rC) and the mismatched analog caused severe diarrhea and nausea at the highest drug concentrations (1 to 4 mg/kg), but poly (ICLC) did not. Each compound also caused depression and lethargy and impaired coordination.
Bacteriostatic and bactericidal activities of 24 antimicrobial agents against Campylobacter fetus subsp. jejuni
Authors: Vanhoof R , Gordts B , Dierickx R , Coignau H , Butzler J P
Published: June 2012

The bacteriostatic and bactericidal activities of 24 antimicrobial agents were tested with the Dynatech MIC 2000 system against 86 strains of Campylobacter fetus subsp. jejuni from human sources. The penicillins (penicillin G, ampicillin, amoxycillin, carbenicillin) had poor activity. Ampicillin and amoxycillin were equally active. Cefotaxime revealed a rather good activity. Erythromycin, gentamicin, tobramycin, amikacin, and furazolidone were the most active compounds. Two strains (2.3%) were resistant to erythromycin. One strain (1.2%) was completely resistant to tobramycin. The tetracyclines (tetracyline, doxycycline, minocycline) were generally effective, but 8% of the strains were totally resistant to them. Minocycline was the most active. Chloramphenicol, thiamphenicol, and clindamycin had good activity. The bacteriostatic and bactericidal distributions for colistin, nalidixic acid, and metronidazole were broad.
New translocation sequence mediating tetracycline resistance found in Escherichia coli pathogenic for piglets
Authors: Jørgensen S T , Oliva B , Grinsted J , Bennett P M
Published: June 2012

A discrete piece of deoxyribonucleic acid coding for tetracycline (Tc) resistance was found to move from one R plasmid to another in an Escherichia coli strain which is pathogenic for piglets. Since this phenomenon took place also in rec strains, the Tc segment was classified as a transposon and called Tn804. Restriction enzyme analysis with EcoRI, BglII, and HindIII indicated that Tn804 is related to Tn10, a well-known transposon that codes for resistance to tetracycline. Hybridization between plasmids carrying the two transposons provided proof of homology between Tn10 and prt of Tn804. Electron microscopic studies showed a transposon-like structure composed of one loop-stem structure with inverted repetitions of approximately 0.9 megadaltons inserted into the loop of a second loop-stem structure. It is suggested that Tn804 is composed of Tn10 plus another transposable sequence.
In vitro effect of rifampin on serum bilirubin determinations
Authors: Meisel S , Pupkoff R , Svaan J
Published: June 2012

An in vitro study demonstrated inerference with the total serum bilirubin assay by toxic rifampin levels. This interference was not observed with therapeutic rifampin levels.
Protection of staphylococci ingested by macrophages from the bactericidal action of rifampin
Authors: Pesanti E L
Published: June 2012

The ability of rifampin to kill Staphylococcus aureus which have been ingested by normal mouse peritoreal macrophages in vitro has been investigated. In contrast to data which have been reported from experiments with other cell types, in this system rifampin was no more active than was penicillin against the two strains tested.
Antibacterial activity of miloxacin
Authors: Izawa A , Kisaki Y , Irie K , Eda Y , Nakagome T , Komatsu T
Published: June 2012

The chemotherapeutic properties of miloxacin (5,8-dihydro-5-methoxy-8-oxo-2H-1,3-dioxolo-[4,5-g]quinoline-7-carboxylic acid) have been compared with those of oxolinic acid and nalidixic acid. The in vitro activities of miloxacin (minimum inhibitory concentrations) against a variety of gram-negative bacteria, especially Enterobacteriaceae and Haemophilus, were comparable to those of oxolinic acid and 8 to 16 times greater than those of nalidixic acid. Miloxacin was more active than oxolinic acid against some anaerobes and less active against staphylococci. Miloxacin exhibited significant activities when administered orally to mice infected with Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, or Serratia marcescens. Its efficacy was comparable to that of oxolinic acid and two to four times greater than that of nalidixic acid. Miloxacin was less active against a Pseudomonas aeruginosa infection and inactive at the maximum test doses against a Streptococcus pyogenes infection.
Determination of miloxacin and metabolites in human serum and urine by high-pressure liquid chromatography
Authors: Yoshitake A , Kawahara K , Shono F , Umeda I , Izawa A , Komatsu T
Published: June 2012

A sensitive and reliable high-pressure liquid chromatography (HPLC) assay for miloxacin and its two principal metabolites, 5,8-dihydro-8-oxo-2H-1,3-dioxolo[4,5-g]quinoline-7-carboxylic acid (M-1) and 1,4-dihydro-1,6-dimethoxy-7-hydroxy-4-oxoquinoline-3-carboxylic acid (M-2), in human serum and urine was developed. A strong anion-exchange Zipax SAX column using a mobile phase of 0.01 M citric acid solution containing 0.03 M sodium nitrate with pH 5.0 was used to achieve separation of the three compounds. The retention times of miloxacin, M-1, and M-2 were 3.8, 9.3, and 5.9 min, respectively. Serum and urine concentrations of these compounds as low as 10 ng/ml were measured. When results from the HPLC assay were compared with those from the microbiological assay of serum and urine samples from human subjects receiving miloxacin orally, the correlation coefficients were 0.94 for the serum and 0.99 for the urine. The HPLC assay method presents an alternative to the microbiological assay and permits future pharmacokinetic investigations of miloxacin.
Antibacterial effect of scandium and indium complexes of enterochelin on Klebsiella pneumoniae
Authors: Rogers H J , Synge C , Woods V E
Published: June 2012

A number of studies point to the conclusion that enterochelin, the iron chelator produced by a number of pathogenic enterobacteria, may be an essential metabolite for bacterial multiplication within the host. The compound removes iron from complexes with the host iron-binding proteins transferrin and lactoferrin, and the resulting ferric enterochelin is assimilated by the bacterial cell. It was reasoned that complexes of enterochelin with ions other than Fe3+ might act as antimetabolites and inhibit bacterial multiplication by interfering with the assimilation of ferric enterochelin. Enterochelin forms complexes with a number of group III and transition metal ions. The complex containing scandium exerts a bacteriostatic effect on Klebsiella pneumoniae in serum, whereas the indium complex induces a large increase in the generation time. The Fe3+ complexes of other microbial iron-transporting compounds are capable of reversing the bacteriostatic effect of the Sc3+ complex of enterochelin, suggesting that the compound acts solely by interfering with the enterochelin system of iron transport. Preliminary experiments show that the Sc3+ complex probably acts as a competitive inhibitor of ferric enterochelin. The Sc3+ complex of enterochelin exerts a therapeutic effect on intraperitoneal K. pneumoniae infections in mice similar to that obtained with kanamycin sulfate.
Characterization of three different beta-lactamases from the Bacteroides fragilis group
Authors: Olsson-Liljequist B , Dornbusch K , Nord C E
Published: June 2012

beta-Lactamases from five strains of Bacteroides fragilis and two strains of Bacteroides uniformis, all resistant to beta-lactam antibiotics, were compared by means of isoelectric focusing and enzyme kinetic measurements. beta-Lactamases from the five B. fragilis strains were identical, whereas those from the two B. uniformis strains were distinguished from each other and also from the B. fragilis enzymes. The two B. uniformis strains were relatively resistant to cefoxitin (minimal inhibitory concentration, 32 micrograms/ml), but only one of the strains, B. uniformis 2986, was found to rapidly inactivate cefoxitin. This apparently enzymatic inactivation of cefoxitin seemed to be of minor importance, and the main factor for cefoxitin resistance was considered to be a decreased permeability of the drug. Transfer of resistance to beta-lactam antibiotics from these beta-lactamase-producing strains of B. fragilis and B. uniformis to a non-beta-lactamase-producing strain of Bacteroides distasonis was attempted, but with these isolates no transfer of resistance to beta-lactam antibiotics was demonstrated.
Chemotherapy of Babesia microti infections in Mongolian Jirds
Authors: Ruebush T K , Contacos P G , Steck E A
Published: June 2012

For identifying drugs which might be effective in the treatment of human Babesia microti infections, 20 selected antiprotozoal agents or combinations of agents were tested for activity against B. microti in Mongolian jirds (meriones unguiculatus). 4-Methyl-primaquine and aromatic diamidines, including diminazene and pentamidine, were the most effective compounds tested.
Ampicillin therapy of experimental enterococcal endocarditis
Authors: Tight R R
Published: June 2012

In rabbits with experimental enterococcal endocarditis, subcutaneously implanted perforated polyethylene chambers were used for ampicillin administration by intra-chamber injection. A total of 21 days of intra-chamber ampicillin therapy sterilized vegetations of 14 out of 14 rabbits with experimental enterococcal endocarditis. In rabbits treated for less than 21 days, the duration of therapy and quantitative vegetation cultures were inversely related. Peak serum minimal bactericidal titers were greater than or equal to 1:8 in 94% of the determinations. Trough serum minimal bactericidal titers were less than or equal to 1:2. The mean trough serum ampicillin concentration (2.6 micrograms/ml) was greater than the minimal bactericidal concentration of ampicillin for the infecting enterococcus and less than the mean trough chamber fluid ampicillin concentration (3.7 micrograms/ml). Relatively prolonged therapy with intrachamber injections seemed to be well tolerated. Combination drug therapy of enterococcal endocarditis may not always be required. The maintenance of serum minimal bactericidal titers greater than or equal to 1:8 throughout the therapy of endocarditis, as is often recommended, may be unnecessary.
Comparison of in vitro activity of Sch 21420, a gentamicin B derivative, with those of amikacin, gentamicin, netilmicin, sisomicin, and tobramycin
Authors: Thornsberry C , Barry A L , Jones R N , Baker C N , Badal R E , Packer R R
Published: June 2012

Sch 21420 is a new aminoglycoside synthesized from gentamicin B. Susceptibility tests with Sch 21420, amikacin, gentamicin, netilmicin, sisomicin, and tobramycin were performed on a variety of bacterial species including 44 with known mechanisms of resistance to aminoglycosides. Sch 21420 and amikacin had similar effects on all except Haemophilus influenzae and Neisseria species, which were more susceptible to amikacin. Except with some strains of Serratia marcescens, the drugs used were bactericidal. Sch 21420 and amikacin were more stable than the other four aminoglycosides in the presence of the inactivating enzymes produced by some strains. Strains which were very resistant to Sch 21420 and emikacin either were permeability mutants or produced AAC (6')-I inactivating enzyme. The effect of cations on the susceptibilities of these strains to Sch 21420 and amikacin was seen mostly with Pseudomonas aeruginosa and to Sch 21420 with Acinetobacter. Cations did not affect the susceptibilities of other Pseudomonas species, Enterobacteriaceae, Staphylococcus aureus, or Streptococcus faecalis to Sch 21420 or amikacin.
Effects of antituberculosis and antileprosy drugs on mycobacteriophage D29 growth
Authors: David H L , Clavel S , Clement F , Moniz-Pereira J
Published: June 2012

The minimal inhibitory concentrations of antituberculosis and antileprosy drugs were determined for Mycobacterium aurum. The concentrations that reduced the final yield of bacteriophage D29R1 by 50% and the time during the replication cycle at which the drugs completely inhibited phage production were estimated. THe 50% inhibitory concentration/minimal inhibitory concentration ratios were close to 1.0 for clofazimine, colistin, rifampin, and streptomycin; these ratios were high for dapsone (diaminodiphenylsulfone) and isoniazid. Ethambutol (minimal inhibitory concentration, 1.0 micrograms/ml) was without effect on viral growth.
Resistance to penicillin and identification of penicillinase-producing Neisseria gonorrhoeae among clinical isolates in Thailand
Authors: Crum J W , Duangmani C , Vibulyasekha S , Suthisomboon K
Published: June 2012

Penicillin-resistant Neisseria gonorrhoeae from 405 patients were studied by determination of penicillin minimal inhibitory concentrations an penicillinase production. Eighteen percent were identified as penicillin-producing N. gonorrhoeae and the mean minimal inhibitory concentration, for all except penicillin-producing strains, was 0.805 micrograms/ml.
Pharmacokinetic studies with dibekacin, a new aminoglycoside, after intravenous and intramuscular administration to human volunteers
Authors: Goto M , Sugiyama M , Ishizaki T
Published: June 2012

The pharmacokinetics of dibekacin, a new aminoglycoside antibiotic, was studied in volunteers given the same dose (100 mg) intramuscularly on two separate occasions and intravenously at two different rates of infusion. The kinetic parameters (t 1/2, 2.24 h, and Vd, 0.136 liter/kg, as the overall mean) observed after intramuscular administration appear to be compatible with those of other aminoglycosides and fairly reproducible within the same individuals. Dibekacin was rapidly absorbed (tmax, 0.84 h), yielding a peak level of 10.4 microgram/ml after the 100-mg intramuscular dose. After the 30- or 60-min infusion, the concentrations of dibekacin in serum fell bi-exponentially, giving an elimination half-life (t 1/2 beta) of 2.50 to 2.88 h. The highest serum levels after th 30- and 60-min infusions were 15.2 +/- 0.9 and 12.1 +/- 1.8 microgram/ml, respectively. Serum levels at 6 h after completion of infusions were 1.9 +/- 0.3 and 1.7 +/- 0.4 microgram/ml, respectively.
5'-Amino-5'-deoxythymidine: synthesis, specific phosphorylation by herpesvirus thymidine kinase, and stability to pH of the enzymically formed diphosphate derivative
Authors: Chen M S , Shiau G T , Prusoff W H
Published: June 2012

Radioactive 5'-amino-5'-deoxythymidine (5'-AdThd), an inhibitor of herpes simplex virus, was synthesized by direct amination of monotosylated thymidine with concentrated ammonium hydroxide. Incubation of 5'-AdThd with purified herpes simplex virus type 1-encoded pyrimidine deoxyribonucleoside kinase produced the diphosphate derivative. The monphosphate derivative of 5'-AdThd was not detected as a reaction product of this enzymatic phosphorylation. A purified mixture of nonviral thymidine kinase and thymidylate kinase derived from uninfected Vero cells was unable to phosphorylate 5'-AdThd under identical conditions. The rate of hydrolysis of 5'-AdThd diphosphate increased as the pH of the reaction mixture decreased, with a shoulder region appearing between pH 3 and 5. The rate of hydrolysis was markedly increased below pH 3. 5'-AdThd, but not the monophosphate derivative, was detected in the hydrolysis mixture. The hydrolysis of 5'-AdThd diphosphate pH 3 also yielded some thymine in addition to 5'-AdThd.
Carbenicillin plus cefazolin with or without mecillinam as an early treatment of bacteremia caused by gram-negative organisms: randomized double-blind study
Authors: Klastersky J , Coppens L , Meunier-Carpentier F , Menday A P
Published: June 2012

Mecillinam or a placebo was added to a combination of cefazolin and carbenicillin as an early therapy of septicemia caused by gram-negative organisms in patients with serious underlying diseases, none of whom was neutropenic, however. Patients in whom infection was caused by pathogens against which mecillinam and cefazolin or mecillinam and carbenicillin were synergistic might have responded more often than patients treated with nonsynergistic combinations. However, overall results did not show any benefit from combining mecillinam with cefazolin and carbenicillin. This study suggests that in nonneutropenic patients with septicemia caused by gram-negative organisms, there is no need to intensify antimicrobial therapy beyond a certain point of efficacy. The measurement of the bactericidal activity in the serum of treated patients might serve as guide for adequate therapy.
Prophylaxis against enterococcal endocarditis: comparison of the aminoglycoside component of parenteral antimicrobial regimens
Authors: Murillo J , Standiford H C , Holley H P , Tatem B A , Caplan E S
Published: June 2012

Prophylactic antibiotics for the prevention of enterococcal endocarditis are recommended for patients with valvular heart disease undergoing surgery or instrumentation of the genitourinary and gastrointestinal tracts. To evaluate the most active aminoglycoside antibiotic to include in these regimens, we administered streptomycin, gentamicin, or amikacin, each in combination with ampicillin, to six healthy adult volunteers in a crossover manner. When the sera from the volunteers were tested for bactericidal activity against 16 strains of enterococci, the gentamicin-ampicillin combination produced higher serum bactericidal levels for a longer duration of time against more strains than the other two regimens. At 1 h after antibiotic administration (a time when surgical procedures are likely to be performed), mean geometric bactericidal titers against the enterococci were 1: 7.0 for the gentamicin-ampicillin regimen, as compared with 1:3.6 and 1:3.2 for the streptomycin-ampicillin and amikacin-ampicillin combinations, respectively. Despite the lower serum levels for gentamicin, we feel that this aminoglycoside should be used in combination with ampicillin for prophylactic regimens against enterococcal endocarditis.
Tentative interpretive criteria for the diffusion susceptibility test using 30-microgram netilmicin disks
Authors: Jones R N , Barry A L , Thornsberry C
Published: June 2012

The disk diffusion inhibitory zone diameters for 10-microgram and 30-microgram netilmicin disks were correlated with minimum inhibitory concentrations against 471 clinical strains tested in cation-supplemented Mueller-Hinton broth. Regression line and error-rate bounded analysis favored the use of 30-microgram netilmicin disks utilizing zone size breakpoints of greater than or equal to 17 mm to indicate susceptibility (less than or equal to 8 microgram/ml) and less than or equal to 13 mm to indicate resistance (greater than 32 microgram/ml). Significant minor interpretive errors may be expected when testing populations of Pseudomonas that have netilmicin minimum inhibitory concentrations near the intermediate range (16 microgram/ml).
Comparison of ceforanide, cefazolin, methicillin, and nafcillin in Staphylococcus aureus endocarditis therapy in rabbits
Authors: Carrizosa J , Kobasa W D , Kaye D
Published: June 2012

Ceforanide (30 mg/kg) administered every 12 h, cefazolin (20 mg/kg) administered every 8 h and methicillin or nafcillin (40 mg/kg) administered every 6 h were equally effective in reducing the number of Staphylococcus aureus in vegetations in rabbits with endocarditis. These treatments were more effective than methicillin or nafcillin administered every 12 h. Ceforanide produced higher peak concentrations and greater bactericidal activity in serum than the other drugs and had the longest half-life (5.8 h, compared with 0.4 to 0.8 h for the other agents.
Effect of beta-lactamase and salt on mecillinam susceptibility of enterobacterial strains
Authors: Bongaerts G P , Bruggeman-Ogle K M
Published: June 2012

Out of 15 selected enterobacterial strains resistant to ampicillin, 12 were able to transfer resistance to mecillinam to Escherichia coli K-12. This resistance to mecillinam was found to be coupled to the presence of beta-lactamase. One strain contained a beta-lactamase characterized as a class IV beta-lactamase, whereas the other 14 strains possessed a class III (TEM-like) beta-lactamase. The specific activity of the class IV beta-lactamase against mecillinam was 55%, and those of the class III beta-lactamase sensitivity of mecillinam, the minimal inhibitory concentrations were lower than might be expected. However, after enzymatic hydrolysis of mecillinam, no antibacterial activity was found. At increasing salt or buffer concentrations the minimal inhibitory concentrations of mecillinam increase to a varying extent for all strains, independently of beta-lactamase production. This study indicates that the increase in minimal inhibitory concentration is dependent on the salt concentration. The study also shows that this increase is not due to salt-mediated hydrolysis or to stimulation either of beta-lactamase activity or of beta-lactamase production. To explain the difference between ampicillin and mecillnam resistance in the beta-lactamase-positive strains, a hypothetical model is presented and discussed.
In vitro antimicrobial activity of rosoxacin against Neisseria gonorrhoeae, Chlamydia trachomatis, and Ureaplasma urealyticum
Authors: Dobson R A , O'Connor J R , Poulin S A , Kundsin R B , Smith T F , Came P E
Published: June 2012

The antimicrobial activity of rosoxacin, a new quinoline antibacterial compound, was determined against the causative organisms of three sexually transmitted diseases. Rosoxacin demonstrated a high degree of activity against Neisseria gonorrhoeae clinical isolates, with the minimal inhibitory concentrations for 50% of these being 0.03 microgram/ml. The corresponding minimal inhibitory concentrations for penicillin, ampicillin, tetracycline, and spectinomycin were 0.25 U/ml, 0.125 microgram/ml, 0.25 microgram/ml, and 16 microgram/ml, respectively. Eleven strains of Chlamydia trachomatis were inhibited by 5 microgram of rosoxacin per ml, and each of seven Ureaplasma urealyticum strains was inhibited by 2 to 8 microgram of rosoxacin per ml. The results of these susceptibility studies, coupled with those of an earlier evaluation of the pharmacokinetics of rosoxacin, provide support for extending or undertaking clinical evaluations of this compound against infections with N. gonorrhoeae, C. trachomatis, and U. urealyticum.
Interaction Between Aminoglycoside Uptake and Ribosomal Resistance Mutations
Authors: Ahmad M. H. , Rechenmacher Angelika , Böck August
Published: June 2012

Mutants resistant to the 2-deoxystreptamine aminoglycosides hygromycin B and gentamicin were analyzed biochemically and genetically. In hygromycin B-resistant strains, ribosomal alterations were not detectable by electrophoretic or genetic experiments. Rather, as was demonstrated for one strain in detail, resistance to this drug seems to be the consequence of several mutations, each impairing drug accumulation, namely of a deletion of a gene close to the
proC
marker which potentiates the effect of a second mutation in the
unc
gene cluster. Three mutants resistant to gentamicin which were previously demonstrated to harbor an altered ribosomal protein, L6, were shown in addition to contain
unc
. Both the
unc
and the ribosomal mutation greatly impair the drug accumulation ability of the mutants. Further evidence for the direct effect of ribosomal mutations on the uptake of aminoglycosides was obtained with strains that possess ribosomes with increased affinity for dihydrostreptomycin. Dihydrostreptomycin transport by these cells is greatly stimulated; thus, the hypersensitivity of these mutants is caused by increased binding affinity for dihydrostreptomycin and its secondary effect on the uptake process. Experiments were also performed on the biochemical basis of the third phase of aminoglycoside transport (acceleration phase). The condition for its onset is that ribosomes are active in protein synthesis irrespective of whether the proteins synthesized are functional. This, and the failure to observe the synthesis of new proteins upon the addition of aminoglycosides, do not support the view of autoinduction of a cognate or related transport system.
Influence of food on absorption of erythromycin ethyl succinate
Authors: Thompson P J , Burgess K R , Marlin G E
Published: June 2012

Erythromycin plasma concentrations were determined in 18 subjects after a single dose (800 mg) of a new formulation of erythromycin ethyl succinate taken immediately before, immediately after, and 1 h after food. Adequate absorption occurred with all treatments, although bioavailability was best when the drug was taken before food. Absorption was delayed by food, with the highest and earliest peak plasma erythromycin levels occurring under fasting conditions.
Effect of N-formimidoyl thienamycin (MK0787) on beta-lactamases and activity against beta-lactamase-producing strains
Authors: Toda M , Sato K , Nakazawa H , Inoue M , Mitsuhashi S
Published: June 2012

N-Formimidoyl thienamycin (MK0787) was active against beta-lactamase-producing strains and was an effective inhibitor of beta-lactamases extracted and purified from these strains except for plasmid-mediated penicillinase type IV.
Uptake of indolmycin in gram-positive bacteria
Authors: Werner R G
Published: June 2012

The antimicrobial activity of indolmycin correlates with the generation time of the investigated strains. Thus, in Staphylococcus aureus ATCC 13150 with a 37-min generation time, the minimal inhibitory concentration (MIC) was 0.6 microgram ml-1, and in Bacillus subtilis ATCC 27142 with a generation time of 23 min, the MIC reached 10.5 micrograms ml-1. Competition experiments in staphylococci and B. subtilis with aromatic amino acids demonstrated that indolmycin uses the uptake systems that are responsible for tryptophan. When the Ki values of indolmycin for the uptake of the aromatic amino acids in staphylococci were compared, there was a significantly higher influence on the uptake of tryptophan with respect to phenylalanine and tyrosine. In addition, indolmycin low resistant mutants of S. aureus ATCC 13150 showed a 10- to 100-fold decrease in Km value for the uptake of tryptophan and a 10-fold decrease for tyrosine uptake. The Km value for phenylalanine remained unchanged. A significant correlation existed between the Ki values of indolmycin for the uptake of tryptophan in the wild-type strains of S. aureus and B. subtilis and the MIC against the corresponding strain. Low Ki values corresponded to low MIC. These results imply that, in addition to improvement of the antibiotic structure for target affinity, the tryptophan uptake system can be used as a test model for the structural evaluation of indolmycin with respect to an increased transport activity into bacterial cells.
Klebsiella species: antimicrobial susceptibilities, bactericidal kinetics, and in vitro inactivation of beta-lactam agents
Authors: Panwalker A P , Trager G M , Porembski P E
Published: June 2012

In vitro properties of 19 antimicrobial agents were tested with 56 isolates of Klebsiella spp. The aminoglycosides and the new beta-lactam compounds cefotaxime and moxalactam were the most inhibitory drugs tested. Chloramphenicol, tetracycline, trimethoprim, and trimethoprim-sulfamethoxazole were moderately active, whereas piperacillin, mezlocillin, and furazlocillin were ineffective against 25% of the isolates. Gentamicin was the only agent tested that was uniformly bactericidal in time-kill experiments with drug concentrations of four times the minimal inhibitory concentration. In combination studies with gentamicin, moxalactam and furazlocillin each increased the rate of bacterial killing for three of five isolates as compared with gentamicin alone, whereas chloramphenicol significantly retarded the rate of bacterial killing for the same number of strains. Furazlocillin was completely inactivated after 24 h of incubation with each of five selected strains. The inactivation of moxalactam, cefoxitin, and cephalothin was 36, 56, and 72%, respectively. In all instances in which these four agents were inactivated to levels below the minimal bactericidal concentration, there was accelerated growth after initial inhibition. However, regrowth also occurred in three instances in which drug levels were higher than the minimal bactericidal concentration. Retesting after drug exposure revealed a 4- to 32-fold rise in the minimal inhibitory concentration and minimal bactericidal concentration in two of these isolates.
Interaction of polyunsaturated fatty acids with animal cells and enveloped viruses
Authors: Kohn A , Gitelman J , Inbar M
Published: June 2012

Essential unsaturated fatty acids such as oleic, linoleic, or arachidonic were incorporated into the phospholipids of animal cells and induced in them a change in the fluidity of their membranes. Exposure of enveloped viruses such as arbo-, myxo-, paramyxo-, or herpesviruses to micromolar concentrations of these fatty acids (which are not toxic to animal cells) caused rapid loss of infectivity of these viruses. Naked viruses such as encephalomyocarditis virus, polio virus or simian virus 40 were not affected by incubation with linoleic acid. The loss of infectivity was attributed to a disruption of the lipoprotein envelope of these virions, as observed in an electron microscope.
Role of the 7 alpha-methoxy and side-chain carboxyl of moxalactam in beta-lactamase stability and antibacterial activity
Authors: Murakami K , Yoshida T
Published: June 2012

The effects of the alpha-carboxyl of the phenylmalonyl side chain and the 7 alpha-methoxy group in moxalactam (6059-S) (7 beta-[2-carboxy-2-(4-hydroxyphenyl) acetamido]-7 alpha-methoxy-3[[(1-methyl-1H-tetrazol-5-y])thio] methyl]-1-oxa-1-dethia-3-cephem-4-carboxylic acid) and in the 1-sulfur congener on the stability to beta-lactamase were investigated by spectrophotometric and microbiological assays. The 7 alpha-methoxy substituent stabilized the compounds against penicillinase hydrolysis, and the alpha-carboxyl group stabilized them against cephalosporinase. An exception is the beta-lactamase produced by Proteus vulgaris, an inducible cephalosporinase, which hydrolyzed compounds having the alpha-carboxyl group but not those having the 7 alpha-methoxy group. Both substituents exerted their stabilizing effects independently, and compounds with both substituents, e.g., moxalactam (6059-S) and its 1-sulfur congener, were resistant to both penicillinases and cephalosporinases. The stabilization of the compounds to beta-lactamase hydrolysis improved their antibacterial activity against beta-lactamase-producing strains.
Limited in vitro activity of cefamandole against 100 beta-lactamase- and non-beta-lactamase-producing Haemophilus influenzae strains: comparison of moxalactam, chloramphenicol, and ampicillin
Authors: Bergeron M G , Claveau S , Simard P
Published: June 2012

In the present study, the minimal inhibitory concentrations and minimal bactericidal concentrations of moxalactam, cefamandole lithium, ampicillin, and chloramphenicol were determined, both in broth and on solid medium, against 75 non-beta-lactamase-producing and 25 beta-lactamase-producing strains of Haemophilus influenzae. Most of the 75 strains were inhibited or killed by 2 microgram or less of ampicillin, chloramphenicol, or moxalactam per ml, but cefamandole exhibited poor bactericidal activity against 11 non-beta-lactamase-producing strains, of which 9 were non-type B H. influenzae. Most of the 25 beta-lactamase-producing H. influenzae were resistant to 128 microgram of ampicillin per ml. Both moxalactam and chloramphenicol, which had minimal inhibitory concentrations of less than 0.25 and 2 microgram/ml, respectively, were more active than cefamandole, which had a minimal inhibitory concentration ranging from 2 to greater than or equal to 128 microgram/ml.
Antibacterial activity of fortimicin A compared with those of five other aminoglycosides, and factors affecting susceptibility tests
Authors: Thornsberry C , Barry A L , Jones R N , Baker C N , Badal R E , Packer R R
Published: June 2012

Fortimicin A, a pseudodisaccharide aminoglycoside, was found to have broad-spectrum activity against most clinically important aerobic and facultatively anaerobic bacteria, except Pseudomonas aeruginosa, some other Pseudomonas species, and streptococci. It was comparable to amikacin in its level of activity (minimum inhibitory concentrations) and spectrum of activity (except for the lack of activity on P. aeruginosa). Fortimicin A was bactericidal and was affected by cations when tested against P. aeruginosa. Minimum inhibitory concentrations were affected by the inoculum used in the susceptibility test. The drug was resistant to most aminoglycoside-inactivating enzymes, but probably is not active against permeability mutants.