bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of inactivation of hepatitis B surface antigen by N alpha-cocoyl-L-arginine ethyl ester
Authors: Sugimoto Y , Toyoshima S
Published: June 2012

The mechanism of N alpha-cocoyl-L-arginine ethyl ester (CAE) in the inactivation of hepatitis B surface antigen (HBsAg) was investigated. The CAE increased the density of HBsAg, and particles of the antigen were destroyed in amorphous clusters, suggesting that CAE influences the lipid components of HBsAg. The lipid components such as cholesterol and phospholipid were mostly removed from the antigen by the treatment with CAE. N alpha-Lauroyl-L-[U-14C] arginine ethyl ester (LAE), a principal component of CAE, became tightly bound to HBsAg in place of the lipid components. The binding amounts of LAE in the HBsAg-LAE complex reached 3.04 +/- 0.44 microgram/mg of protein. The formation of the complex was not influenced by the presence of CAE-related compounds such as L-arginine, L-arginine ethyl ester, and N alpha-cocoyl-L-arginine. Treatment with mercaptoethanolurea, guanidine hydrochloride, and some detergents failed to resolve appreciably the labeled LAE from the labeled complex. All attempts to reactivate the CAE-treated HBsAg and to restore it morphologically from the denatured aggregates were unsuccessful. These results indicate that CAE tightly binds to HBsAg, followed by formation of stable aggregates of the denatured HBsAg-CAE complex.
Epimers of moxalactam: in vitro comparison of activity and stability
Authors: Wise R , Wills P J , Bedford K A
Published: June 2012

Moxalactam exists in two epimeric forms, R and S. The in vitro activity of these two epimers was compared with that of material available for clinical and laboratory use (R + S moxalactam). Generally, R moxalactam was twice as active as the S form. The stability of R + S moxalactam was studied at 37, 20, 4 and -20 degrees C in buffer and serum. Only in serum at 37 degrees C was there any appreciable loss of activity (half-life, 8 h). The stability of R and S epimers was studied separately, and the composition of the resulting equilibrium was investigated. At 37 degrees C in serum, one-half of the excess of either R or S over the equilibrium mixture was converted into the equilibrium mixture in 1.5 h. The proportions of R to S in an equilibrium mixture in buffer were 50:50, but in serum they were 45:55. It is doubtful whether these differences in stability and activity will have any significant clinical importance.
Beta-lactamase stability and antibacterial activity of cefmenoxime (SCE-1365), a novel cephalosporin
Authors: Okonogi K , Kuno M , Kida M , Mitsuhashi S
Published: June 2012

Cefmenoxime, a new cephalosporin antibiotic, has been shown to be stable to a Staphylococcus aureus penicillinase and R plasmid-mediated type I and type IV penicillinases. It was also resistant to hydrolysis by most cephalosporinases, but was susceptible to hydrolysis by a Proteus vulgaris beta-lactamase. Cefmenoxime was active against cephaloridine-resistant species, except Pseudomonas aeruginosa, which was moderately resistant to cefmenoxime. Cefmenoxime was an inducer of P. vulgaris beta-lactamase biosynthesis, but 1 microgram or more of the drug per ml, which inhibits most of the clinical isolates of P. vulgaris, was required for the production of detectable amounts of the enzyme. Cefmenoxime was a strong competitive inhibitor of beta-lactamases of Enterobacter cloacae, Citrobacter freundii, P. aeruginosa, and Serratia marcescens, but it did not inhibit penicillinases in spite of its resistance to hydrolysis.
Mezlocillin: tentative interpretive standards for disk diffusion susceptibility testing
Authors: Fuchs P C , Barry A L , Thornsberry C , Jones R N , Gerlack E H
Published: June 2012

The susceptibility of 447 clinical bacterial isolates to mezlocillin and carbenicillin was tested by standardized agar disk diffusion and reference broth micro-dilution methods. Tentative interpretive criteria for disk susceptibility testing by using 75 micrograms mezlocillin disks are proposed: susceptible, greater than or equal to 16 mm; indeterminate, 13 to 15 mm; and resistant, less than or equal to 12 mm. These would be applicable to both Pseudomonas species and the Enterobacteriaceae, but not to Staphylococcus aureus. For S. aureus, the breakpoints for susceptible, greater than or equal to 29 mm, and resistant, less than or equal to 28 mm, hold for mezlocillin as well as for the other penicillinase-susceptible penicillins.
Susceptibility of Haemophilus influenzae to chloramphenicol and eight beta-lactam antibiotics
Authors: Thirumoorthi M C , Kobos D M , Dajani A S
Published: June 2012

We examined the minimal inhibitory concentrations and minimal bactericidal concentrations of chloramphenicol, ampicillin, ticarcillin, cefamandole, cefazolin, cefoxitin, cefotaxime, ceforanide, and moxalactam for 100 isolates of Haemophilus influenzae, 25 of which produced beta-lactamase. Susceptibility was not influenced by the capsular characteristic of the organism. The mean minimal inhibitory concentrations of cefamandole, ticarcillin, and ampicillin for beta-lactamase-producing strains were 3-, 120-, and 400-fold higher than their respective mean minimal inhibitory concentrations for beta-lactamase-negative strains. No such difference was noted for the other antibiotics. We performed time-kill curve studies, using chloramphenicol, ampicillin, cefamandole, cefotaxime, and moxalactam with two concentrations of the antimicrobial agents (4 or 20 times the minimal inhibitory concentrations) and two inoculum sizes (10(4) or 10(6) colony-forming units per ml). The inoculum size had no appreciable effect on the rate of killing of beta-lactamase-negative strains. The rates at which beta-lactamase-producing strains were killed by chloramphenicol, cefotaxime, and moxalactam was not influenced by the inoculum size. Whereas cefamandole in high concentrations was able to kill at 10(6) colony-forming units/ml of inoculum, it had only a temporary inhibiting effect at low drug concentrations. Methicillin and the beta-lactamase inhibitor CP-45,899 were able to neutralize the inactivation of cefamandole by a large inoculum of beta-lactamase-producing H. influenzae.
Susceptibility of group A beta-hemolytic Streptococcus isolates to penicillin and erythromycin
Authors: Istre G R , Welch D F , Marks M I , Moyer N
Published: June 2012

We have reevaluated the antibiotic susceptibilities of group A beta-hemolytic streptococci in view of recent reports of a high prevalence of erythromycin resistance in Japan and of an increase in penicillin treatment failures in the United States. A total of 474 isolates recovered during a 2- to 3-month period in 1980 were tested. All were susceptible by microtiter broth dilution to a penicillin concentration of less than or equal to 0.03 micrograms/ml (minimal inhibitory concentration), and 473 were killed by less than or equal to 0.06 micrograms/ml (minimal inhibitory concentration). Erythromycin minimal inhibitory concentrations showed a bimodal distribution: 95% were less than or equal to 0.06 micrograms/ml, and 5% were greater than or equal to 1 microgram/ml. Of the minimal bactericidal concentrations, 21% were greater than or equal to 1 microgram/ml and 3% were greater than or equal to 16 micrograms/ml. Group A beta-hemolytic streptococci remain susceptible to the inhibitory and bactericidal actions of penicillin, thus providing no in vitro explanation for the bacteriological relapses reported in some clinical studies. Unlike the Japanese experience, only 5% of our isolates were resistant to erythromycin (minimal inhibitory concentration, greater than or equal to 1 microgram/ml); however, 22% were tolerant (ratio of minimal inhibitory/bactericidal concentrations, greater than or equal to 32).
In vitro studies with Win 42122-2: comparison with gentamicin, netilmicin, and amikacin
Authors: Sanders C C , Sanders W E
Published: June 2012

The in vitro activity of Win 42122-2 against gram-negative clinical isolates was compared in serial twofold broth dilution tests with gentamicin, netilmicin, and amikacin. Against 173 gentamicin-susceptible Enterobacteriaceae, the activity of Win 42122-2 was generally twofold less than those of gentamicin or netilmicin and similar to that of amikacin. Against 60 gentamicin-susceptible nonfermentative gram-negative bacilli, including P. aeruginosa, the activity of Win 42122-2 was four- to eightfold less than that of gentamicin or netilmicin and two- to fourfold less than that of amikacin. Minimal bacterial concentrations for Win 42122-2 were usually similar to minimal inhibitory concentrations. Win 42122-2 was not highly active against gentamicin-resistant bacteria. Win 42122-2 was as active as gentamicin against Mycobacterium tuberculosis but was less active than gentamicin or amikacin against atypical mycobacteria. Win 42122-2 interacted synergistically with penicillin G against enterococci, including strains highly resistant to streptomycin.
Effects of Aminoglycoside Antibiotics on Neutrophil Chemotaxis
Authors: Sacchi Fulvio , Marseglia Gianluigi , Fietta Anna , Marchi Antonietta , Siccardi Antonio G.
Published: June 2012

The inhibitory effect of neutrophil chemotaxis of gentamicin, tobramycin, and sisomicin was shown. The combined effect of aminoglycosides and histamine was not additive.
Antagonism of ampicillin and chloramphenicol for meningeal isolates of group B streptococci
Authors: Weeks J L , Mason E O , Baker C J
Published: June 2012

The increasing prevalence of ampicillin-resistant Haemophilus influenzae type b has led to the recommendation that ampicillin and chloramphenicol be given as the initial therapy for suspected bacterial meningitis in infants and children. However, during the first 2 months of life, H. influenzae type b is a rare cause of meningitis, whereas group B streptococcus is the most frequently isolated agent. Since ampicillin and chloramphenicol have been shown to be antagonistic for other streptococci, an in vitro study of their effect on group B streptococci was performed. The effect of ampicillin and chloramphenicol, alone and in combination, on 18 meningeal isolates was determined for 2 different inocula of group B streptococci, using microtiter broth dilution and growth kinetic assays. Isoboles, fractional lethal concentration indices, or both indicated antagonism for all strains. Growth kinetic assays for two representative strains demonstrated inhibition of the early bactericidal activity of ampicillin by chloramphenicol. These findings of in vitro antagonism suggest that this combination may be contraindicated for the treatment of infants with group B streptococcal meningitis.
Resistance to tetracycline, erythromycin, and clindamycin in the Bacteroides fragilis group: inducible versus constitutive tetracycline resistance
Authors: Privitera G , Fayolle F , Sebald M
Published: June 2012

The transferability of plasmid-mediated tetracycline, erythromycin, and clindamycin resistance was studied in 63 clinical isolates of the Bacteroides fragilis group. Of 48 strains which were tetracycline resistant (Tcr), the regulation of both the expression of Tcr and its transferability was shown to be under inducible control by tetracycline. In 29 of the strains, Tcr was transferable; in the majority of these (26 strains), transferability was inducible (Trai) and it was constitutive (Trac) in only 3 strains. All four possible phenotypes were found (Tci Trai, Tci Trac, Tcc Trai, and Tcc Trac), which indicates independent control of both Tcr expression and its transferability. Resistance to erythromycin and clindamycin was cotransferred with Tcr in 14 of the 48 Tcr strains and transferred independently of Tcr in only 1 strain.
Mutagenicity of quindoxin, its metabolites, and two substituted quinoxaline-di-N-oxides
Authors: Beutin L , Preller E , Kowalski B
Published: June 2012

The quinoxaline-di-N-oxides carbadox, olaquindox, and quindoxin, which are potent antibacterial agents, were tested for mutagenicity in the Salmonella microsomal system. They all induced base pair substitutions and frameshift mutations in Salmonella, and occurred independently of the presence of a rat liver microsomal fraction in the test system. Mutagenicity was dependent on the presence of their N-oxide groups, since quinoxaline, a completely reduced derivative of quindoxin, was not mutagenic, whereas the partially reduced quinoxaline-N-oxide exhibited a lower mutagenic activity than quindoxin. recA and uvrB Salmonella were found to be more susceptible to mutagenic quinoxaline derivatives than wild-type strains. The mutagenicity of quinoxaline-di-N-oxides was enhanced under anaerobic incubation as was the antibacterial activity. These results suggest that both the antibacterial and mutagenic activity of quinoxaline-di-N-oxides depend upon the same bacterial activation mechanism.
Aminoglycoside phosphotransferase-II-mediated amikacin resistance in Escherichia coli
Authors: Bongaerts G P , Kaptijn G M
Published: June 2012

An Escherichia coli strain with a plasmidic amikacin resistance has been selected for which the evidence strongly indicates that resistance is mediated by aminoglycoside phosphotransferase [APH(3')-II]: (i) this resistance was coupled with resistance against kanamycin and neomycin; (ii) partially purified APH(3')-II[APH(3") free] modified amikacin by phosphorylation; (iii) the product of the APH(3')-II mediated reaction (i.e., 3'-O-phosphoryl-amikacin) lost its antibacterial activity; and (iv) the amikacin-modifying APH(3')-II activity increased 5- to 10-fold after adaptation of the cells to higher concentrations of amikacin. The substrate spectrum of this enzyme showed a low activity against amikacin as compared with neomycin. It is argued that the enzyme level rather than its substrate spectrum is important for enzyme-mediated resistance. The increase in enzyme levels was found to be correlated with an increase in copy number of a 110-Megadalton plasmid (pBN66) which coded for the APH(3')-II and the APH(3") activity. The increase in copy number was irreversible, and therefore this phenomenon is ascribed to a mutation of a gene which affects the copy number. In transconjugants, the original low copy number was present, and therefore the mutation must be located on the chromosome and not on the plasmid.
Comparison of ceftazidime and cefamandole pharmacokinetics and blister fluid concentrations
Authors: Armstrong G C , Wise R , Brown R M , Hancox J
Published: June 2012

Eight healthy male volunteers received 1 g of either ceftazidime or cefamandole as an intravenous infection. Serial blood samples were taken over the next 8 h. Urine samples were collected over 24 h. Levels of these antibiotics were measured in the fluid of blisters resulting from application of cantharides. The concentration of ceftazidime in serum at 0.25 h after intravenous injection was 83.3 micrograms/ml. The serum half-lives for the respective drugs were 1.8 and 0.8 h. The mean apparent volume of distribution of ceftazidime (13.6 liters) was greater than that of cefamandole (9.8 liters). Plasma clearance was 111 ml/min for ceftazidime and 216 ml/min for cefamandole. The maximum blister fluid concentration of ceftazidime was 45.9 micrograms/ml, and that of cefamandole was 22.1 micrograms/ml. The relative availability of each drug in blister fluid compared with serum was similar.
Pharmacokinetics, protein binding, and predicted extravascular distribution of moxalactam in normal and renal failure subjects
Authors: Peterson L R , Bean B , Fasching C E , Korchik W P , Gerding D N
Published: June 2012

Ten normal subjects and ten patients with chronic renal failure requiring hemodialysis were given intravenous infusions of moxalactam ranging from 500 mg to 2 g. Serum and urine concentrations were measured for up to 12 h. Renal failure subjects were given doses both during and between hemodialysis treatments. Protein binding of moxalactam in both normal and uremic serum was determined by ultracentrifugation. The serum half-life in normal subjects was 2.1 and 2.3 h for the 1- and 2-g doses, respectively. The half-life of moxalactam in patients with renal failure was 13.9 h on the 500-mg dose and 13.3 h on the 1.0-g dose. During hemodialysis the serum half-life fell to 4.4 and 5.7 h, respectively. Moxalactam protein binding ranged from 52% in normal serum to 36% in renal failure patient serum. Unbound moxalactam appeared to distribute with the entire body water based on the serum pharmacokinetics and antibiotic serum protein binding determined in this study.
Effects of ethambutol on accumulation and secretion of trehalose mycolates and free mycolic acid in Mycobacterium smegmatis
Authors: Kilburn J O , Takayama K
Published: June 2012

We examined the early effects of ethambutol on the synthesis of trehalose monomycolate, trehalose dimycolate, and free mycolic acid in actively growing cells of Mycobacterium smegmatis. At about 1 min after the addition of 3.0 micrograms of ethambutol per ml, the cellular level of trehalose monomycolate began to increase over the control culture. This was followed 8 to 12 min later by the cellular increases in free mycolic acid and trehalose dimycolate over the control culture and the inhibition of incorporation of mycolic acid into the cell wall. Exposure of M. smegmatis to ethambutol for more than 30 min caused all of these lipids to leak out of the cells more rapidly than in the control cells. The mechanism by which ethambutol initiates these events is unknown, but these early imbalances in lipid synthesis may be responsible for the lethal action of this drug.
Mezlocillin Enteral Absorption in Rabbits
Authors: Lavelle Kevin J. , Brier Michael E. , Aronoff George R.
Published: June 2012

To determine the role of enterohepatic recirculation on its nonlinear elimination, we studied the enteral absorption of mezlocillin in rabbits. Mezlocillin was not substantially absorbed from the stomach or duodenum. We conclude that enterohepatic recirculation does not cause the dose-dependent elimination kinetics of mezlocillin.
Mode of action of the copper(I) complex of 2,9-dimethyl-1,10-phenanthroline on Mycoplasma gallisepticum
Authors: Smit H , van der Goot H , Nauta W T , Timmerman H , de Bolster M W , Jochemsen A G , Stouthamer A H , Vis R D
Published: June 2012

Various physiological important activities of Mycoplasma gallisepticum were inhibited by the copper(I) complex of 2,9-dimethyl-1,10-phenanthroline [Cu(DMP)2NO3]. The energy-yielding metabolism was inhibited because the conversion of pyruvate into lactate was found to be blocked by Cu(DMP)2NO3, indicating a selective inhibition of lactate dehydrogenase. Also, the production rate of acetate and the rate of oxygen uptake by whole cells of M. gallisepticum appeared to be strongly decreased. Experiments with crude cell extracts showed an inhibition of reduced nicotinamide adenine dinucleotide (NADH) oxidase by Cu(DMP)2NO3 and an even stronger inhibition of NADH oxidase and lactate dehydrogenase by CuSO4. No preferential inhibition of adenosine 5'-triphosphatase and pyruvate kinase was found. Investigations on the influence of Cu(DMP)2NO3 on deoxyribonucleic acid, ribonucleic acid, and protein synthesis with growing cells of M. gallisepticum showed a selective inhibition of the incorporation of [14C]thymidine into deoxyribonucleic acid. Cu(DMP)2NO3 induced a decrease in the total amount of accessible sulfhydryl groups of whole cells of M. gallisepticum, indicating that the observed diverse toxicity of Cu(DMP)2NO3 may be associated with the interaction of copper ions with protein sulfhydryl groups.
Clinical Pharmacology of Cefotaxime in Pediatric Patients
Authors: Kafetzis Dimitris A. , Brater D. Craig , Kanarios John , Sinaniotis Constantine A. , Papadatos Constantine J.
Published: June 2012

Cefotaxime is a new cephalosporin with a spectrum of activity which may make it appropriate for use in pediatric patients. In 33 infants and children, administration of cefotaxime resulted in cure or improvement in 97% of patients, with eradication of 94% of isolated pathogens. Toxicity was minimal. The disposition of cefotaxime in this age group was similar to that reported for adults, with an elimination half-life of approximately 1.5 h, a volume of distribution of 1 liter/kg, a total serum clearance of 10 ml/min per kg, and a renal clearance of 6 ml/min per kg.
Inhibition of bluetongue and Colorado tick fever orbiviruses by selected antiviral substances
Authors: Smee D F , Sidwell R W , Clark S M , Barnett B B , Spendlove R S
Published: June 2012

The effects of four ribonucleic acid virus inhibitors were evaluated in cell cultures and in mice to determine inhibitory effects against bluetongue virus and Colorado tick fever virus (CTFV). Test compounds included 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin), 3-deazaguanine, 3-deazauridine, and 9-(S)-(2,3-dihydroxypropyl)adenine. Ribavirin-2',3',5'-triacetate (ribavirin triacetate) was evaluated in vivo against CTFV. Inhibition of cytopathic effect and plaque reduction were used to evaluate antiviral activity. In cytopathic effect inhibition studies, bluetongue virus was markedly inhibited by 3-deazaguanine and 3-deazauridine in Vero cells with moderate inhibition by the other agents. Ribavirin and 3-deazaguanine markedly inhibited CTFV in MA-104 cells, 3-deazauridine was slightly less active, and 9-(S)-(2,3-dihydroxypropyl)adenine was negative. Ribavirin was less effective in Vero cells against CTFV. When mice were inoculated intracerebrally with CTFV and treated by a single intracerebral injection with drug, ribavirin triacetate increased the number of survivors, 3-deazaguanine increased mean survival time, and ribavirin was negative. Intraperitoneal treatment of infected mice with ribavirin triacetate for 1 week significantly increased the number of survivors and mean survival time, providing strong evidence that the agent is active across the blood-brain barrier.
Mutants of
Escherichia coli
That Are Resistant to Certain Beta-Lactam Compounds Lack the
ompF
Porin
Authors: Harder Karen J. , Nikaido Hiroshi , Matsuhashi Michio
Published: June 2012

Carbenicillin-resistant mutants of
Escherichia coli
K-12 and B/r were found to produce greatly diminished levels of the porin coded by the
ompF
gene. Physiological and ecological implications of these findings are discussed.
Susceptibility of Gram-Positive Cocci to Various Antibiotics, Including Cefotaxime, Moxalactam, and
N
-Formimidoyl Thienamycin
Authors: Cherubin Charles E. , Corrado Michael L. , Sierra Marcelino F. , Gombert Myles E. , Shulman Michael
Published: June 2012

The activities of cefotaxime, moxalactam, MK 0787 (
N
-formimidoyl thienamycin), ampicillin, oxacillin, vancomycin, and clindamycin were compared against gram-positive cocci. MK 0787 was the most active and moxalactam was the least active of these drugs, except against methicillin-resistant
Staphylococcus aureus
, where vancomycin was most active, and penicillin-resistant pneumococci, where cefotaxime was more active.
Mezlocillin disposition in chronic hemodialysis patients
Authors: Janicke D M , Mangione A , Schultz R W , Jusko W J
Published: June 2012

The pharmacokinetics of a single 1-g intravenous dose of mezlocillin were examined in six functionally anephric patients undergoing hemodialysis. Hemodialysis clearance calculated by plasma extraction ratios across the dialyzer membrane and by dialysis fluid agree well, averaging 26 and 32 ml/min. Dialyzer extraction ratios averaged 0.16 +/- 0.07, and 23.3 +/- 9.6% of the dose was measured in the dialysate. Plasma clearances (104 +/- 45 ml/min) and steady-state volumes of distribution (0.22 +/- 0.07 liter/kg) of mezlocillin showed good agreement with literature values. The nonrenal clearance (4.25 +/- 2.30 liters/h per 1.73 m2) of mezlocillin was appreciable. Drug loss by hemodialysis is small and should have little effect on therapeutic dosage needs.
Chronic Salmonella bacteriuria with intermittent bacteremia treated with low doses of amoxicillin or ampicillin
Authors: Bassily S B , Kilpatrick M E , Farid Z , Mikhail I A , El-Masry N A
Published: June 2012

Amoxicillin and ampicillin were compared at a dose of 250 mg twice daily for 4 weeks to treat Salmonella typhi or Salmonella paratyphi A chronic bacteriuria with intermittent bacteremia. Eleven patients received amoxicillin, and 15 received ampicillin. Concentrations of the two drugs were measured in the urine and serum on treatment days 1, 2, and 7. The urine levels of both antibiotics were maximal 2 h after administration, and minimal levels were 80-fold higher than the S. typhi minimal inhibitory concentration and 20-fold higher than the S. paratyphi A minimal inhibitory concentration. The serum level of amoxicillin was below the minimal inhibitory concentration of S. paratyphi A 6 h after administration on each of the testing days. The serum antibiotic levels of the two drugs showed no cumulative effect at day 2 or day 7. Of the 11 patients treated with amoxicillin, 1 had positive urine cultures during treatment, and 1 treated with ampicillin continued to be symptomatic.. Recurrence of bacteriuria occurred in three of seven patients with persistent bladder calcification. None of the 26 patients in this study had positive blood culture during or after treatment. Amoxicillin and ampicillin at a dose of 250 mg twice daily were equally successful in treating chronic salmonelluria.
Comparative in vitro activity of cefmenoxime, cefotaxime, cefuroxime, cefoxitin, and penicillin against Neisseria gonorrhoeae
Authors: Khan M Y , Siddiqui Y , Simpson M L , Gruninger R P
Published: June 2012

The in vitro activity of a new beta-lactam antibiotic, cefmenoxime, was compared with those of cefotaxime, cofuroxime, cefoxitin, and penicillin against 72 beta-lactamase-negative and 26 beta-lactamase-positive Neisseria gonorrhoeae. Cefmenoxime was as active as cefotaxime and more active than the other three antimicrobial agents. It inhibited all isolates, regardless of beta-lactamase activity, at a concentration of less than or equal to 0.015 microgram/ml.
Comparative in vitro activity of ceftizoxime, cefoperazone, and cefoxitin against anaerobic bacteria
Authors: Drulak M W , Chow A W
Published: June 2012

Against 482 obligate anaerobes studied by the agar dilution technique, ceftizoxime was significantly more active than both cefoxitin and cefoperazone (P less than 0.001); the latter two agents were comparable in activity. The enhanced activity of ceftizoxime, as compared with the activity of cefoxitin, was against both gram-positive and gram-negative anaerobes (especially Lactobacillus and bacteroides spp). Cefoperazone, however, was more active than cefoxitin against gram-positive anaerobes (particularly Lactobacillus spp.) but was less active than cefoxitin against gram-negative anaerobes (particularly Bacteroides fragilis and Veillonella spp.).
Effect of Filtration on Antimicrobial Solutions
Authors: Murray Patrick R. , Niles Ann C.
Published: June 2012

The effect of filtering 20 antimicrobial solutions through four types of membrane filters was examined. Essentially, all antimicrobial activity was recovered after the solutions were filtered.
Antimicrobial Susceptibility of Intracellular
Legionella pneumophila
Authors: Bacheson Margaret A. , Friedman Harvey M. , Benson Charles E.
Published: June 2012

Minimum inhibitory concentrations, minimum bactericidal concentrations, and killing curve assays were measured after
Legionella pneumophila
was grown in human lung fibroblasts. Results of susceptibility testing of organisms grown intracellularly are compared with results for organisms grown by standard tube dilution methods.
Superior activity of N-formimidoyl thienamycin against gentamicin-resistant Pseudomonas aeruginosa
Authors: Michael P R , Alford R H , McGee Z A
Published: June 2012

N-Formimidoyl thienamycin (N-F-thienamycin), cefotaxime, moxalactam, and cefsulodin were tested by agar dilution against 125 isolates of Pseudomonas aeruginosa, Serratia marcescens, Klebsiella pneumoniae, and Providencia stuartii. Against gentamicin-susceptible P. aeruginosa, N-F-thienamycin and cefsulodin were most active. Only N-F-thienamycin inhibited gentamicin-resistant P. aeruginosa at less than or equal to 4 microgram/ml. N-F-thienamycin's activity equaled or surpassed that of the other antibiotics tested against both the gentamicin-susceptible and -resistant Enterobacteriaceae.
Factors affecting the in vitro activity of cefoperazone against the Bacteroides fragilis group
Authors: Sutter V L , Kwok Y Y
Published: June 2012

The in vitro activity of cefoperazone against 32 strains of bacteria of the Bacteroides fragilis group was determined on four media by using a variety of test parameters. Lower mean minimal inhibitory concentrations (MICs) were obtained on Mueller-Hinton blood agar and supplemented brain heart infusion agar than were obtained on brucella laked blood agar or Wilkins-Chalgren agar. Higher MICs were obtained with 6-h inocula than with 24-h inocula, and slightly higher MICs were obtained with tests read at 48 as compared with 24 h. Conducting tests in an anaerobic glove box had little effect. The greatest differences in mean MICs were seen with inoculum densities of 10(4) and 10(5) colony-forming units.
Metabolic inhibition of Peptostreptococcus anaerobius decreases the bactericidal effect of hydrogen peroxide
Authors: Nyberg G K , Carlsson J
Published: June 2012

Peptostreptococcus anaerobius VPI 4330-1 was tested under various conditions for examination of the bactericidal effect of hydrogen peroxide. The cells were most rapidly killed by hydrogen peroxide when they were in the exponential-growth phase. Cooling or starving the cells decreased the bactericidal effect of hydrogen peroxide. The ionophore nigericin and the metal ion chelating agent 2,2'-bipyridine stopped macromolecular syntheses and greatly decreased the bactericidal effect of hydrogen peroxide. The ionophore valinomycin and the glycolytic inhibitor iodoacetate also stopped the syntheses of the macromolecules but only slightly decreased the bactericidal effect of hydrogen peroxide. Novobiocin, an inhibitor of deoxyribonucleic acid gyrase, and chloramphenicol, an inhibitor of protein synthesis, were not able to decrease the bactericidal effect of hydrogen peroxide. These findings implicate metal ions and an active metabolism of the organism in the bactericidal effect of hydrogen peroxide.
Effect of clindamycin prophylaxis on the colonic microflora in patients undergoing colorectal surgery
Authors: Kager L , Liljeqvist L , Malmborg A S , Nord C E
Published: June 2012

Clindamycin was given intravenously to 15 patients undergoing colorectal surgery in an initial dose of 600 mg, given at induction of anesthesia followed by 6 doses of 600 mg at 8-h intervals. Series of serum samples and fecal specimens were taken for analysis of clindamycin concentrations. Tissue samples from the gut wall were taken at surgery. The highest serum concentrations observed occurred 30 min after administration of clindamycin and varied between 6.8 and 37.9 microgram/ml (mean, 14.8 +/- 2.0 [standard error] microgram/ml). The clindamycin concentrations in the tissue samples were between 1.8 and 13.0 microgram/g. Clindamycin concentration in the fecal samples varied between 2.1 and 460 microgram/g. Fecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. Among the aerobic bacteria, enterococci and streptococci decreased during the prophylaxis period. Anaerobic bacteria also decreased significantly during the same period. After the clindamycin administration period, enterococci, streptococci and anaerobic bacteria proliferated. No anaerobic strains resistant to clindamycin were isolated. Postoperative infections due to Streptococcus faecalis and different enterobacteria such as Escherichia coli, Enterobacter cloacae, Citrobacter freundii, and Klebsiella occurred in five patients.
Cefmenoxime (SCE-1365), a new Cephalosporin: In Vitro Activity, Comparison with Other Antimicrobial Agents, Beta-Lactamase Stability, and Disk Diffusion Testing with Tentative Interpretive Criteria
Authors: Fuchs Peter C. , Jones Ronald N. , Thornsberry Clyde , Barry Arthur L. , Gerlach E. Hugh , Sommers Herbert M.
Published: June 2012

The in vitro activity of cefmenoxime (SCE-1365) was evaluated in a multiphased collaborative investigation. Over 7,500 consecutive clinical isolates were tested in five laboratories, and greater than 90% of the following organisms were inhibited by cefmenoxime at the following concentrations:
Enterobacteriaceae
and non-enterococcal streptococci, ≤0.125 μg/ml;
Staphylococcus aureus
, ≤2.0 μg/ml; and nonfermenting gram-negative bacilli and
Bacteroides fragilis
group, ≤32 μg/ml. Both beta-lactamase-producing and -nonproducing
Haemophilus influenzae
and
Neisseria gonorrhoeae
were inhibited by cefmenoxime at ≤0.03 μg/ml. The spectrum of cefmenoxime was similar to that of other, newer cephalosporins, particularly cefotaxime. A pronounced inoculum effect was found with some species upon increasing inocula from 10
5
to 10
7
colony-forming units per ml, resulting in an approximate eightfold increase in minimum inhibitory concentrations. Cefmenoxime was bactericidal when tested with inocula of 10
5
colonyforming units per ml, and mean differences between the minimum inhibitory concentration and the minimum lethal concentration were less than one log
2
dilution. No significant hydrolysis of cefmenoxime by five different beta-lactamases was detectable, and cefmenoxime exhibited marked inhibition of type I beta-lactamases. Regression and error rate-bounded analyses of results of disk diffusion and reference broth microdilution susceptibility tests were performed on 421 bacterial isolates, and the following tentative zone size breakpoints are proposed: ≥22 mm, susceptible; ≤14 mm, resistant; and 15 to 21 mm, moderately susceptible (indeterminate). These data and cross-resistance studies with other newer cephalosporins indicate marked similarity of in vitro activity within this group of drugs, particularly between cefmenoxime, moxalactam, and cefotaxime. Any one of these could serve as the representative for the disk diffusion testing of this group of drugs if comparable minimum inhibitory concentration breakpoints were used for each drug.
Laboratory evaluation of the Anderson Technical semiautomated susceptibility testing system
Authors: McKinley G A , Fagerberg D J , George B A
Published: June 2012

Anderson Technical, Inc. has developed rapid, semiautomated equipment for antimicrobial susceptibility testing. A total of 310 fresh clinical bacterial isolates (226 gram-negative and 75 gram-positive) were tested with the Anderson Technical system and compared with those of Micro-Media Systems, Inc. For the gram-positive organisms, 74.3% of the test pairs had identical minimum inhibitory concentration values, whereas 99.1 and 0.9% of the test pairs had minimal inhibitory concentration values differing by less than or equal to 1 and greater than 1 dilution level, respectively. Identical minimum inhibitory concentration values were obtained for 67.2% of the gram-negative test pairs, whereas 97.6 and 2.4% differed by less than or equal to 1 and greater than 1 dilution level, respectively. For all organisms tested, 98.0% differed by less than or equal to 1 dilution level. The Anderson Technical equipment proved to be a rapid and flexible system for microdilution testing.
Influence of serum protein binding and mode of administration on penetration of five cephalosporins into subcutaneous tissue fluid in humans
Authors: Hoffstedt B , Walder M
Published: June 2012

The penetration of five cephalosporins into interstitial fluid was investigated by a new method employing cotton threads implanted subcutaneously. Penetration after short bolus injections, calculated as area under interstitial fluid level curve divided by area under serum level curve x 100, was 47.0% for cephradine, 30.6% for cefuroxime, 26.7% for cefotaxime, 24.6% for cefoxitin, and 9.6% for cefoperazone. There was an inverse correlation between the degree of penetration and serum protein binding with r = -0.97. The area under interstitial fluid level curves was the same whether the drugs were administered as short bolus injections or short time infusions.
Amoxicillin-clavulanic acid in treatment of urinary tract infection due to gram-negative bacteria resistant to penicillin
Authors: Martinelli R , Lopes A A , de Oliveira M M , Rocha H
Published: June 2012

Twenty-two adult patients with urinary tract infections caused by penicillin-resistant bacteria completed treatment with amoxicillin alone or amoxicillin plus clavulanic acid in a randomized double-blind clinical trial. Of the 13 patients treated with amoxicillin plus clavulanic acid, the absence of bacteriuria within 7 days of therapy was observed in 85%, as compared with only 25% of the 8 patients receiving amoxicillin only. There were no significant side effects nor any clinical, biochemical, or hematological abnormalities related to either treatment. It was concluded that the combination of clavulanic acid and amoxicillin could be useful in the treatment of uncomplicated urinary tract infection caused by penicillin-resistant bacteria.
Interaction of metronidazole with resistant and susceptible Bacteroides fragilis
Authors: McLafferty M A , Koch R L , Goldman P
Published: June 2012

The kinetics of the lethal action of metronidazole and the formation of acetamide have been studied in a strain of Bacteroides fragilis which is relatively resistant to metronidazole. As with a susceptible strain of B. fragilis, the data are consistent with a model in which a labile intermediate in metronidazole metabolism interacts either with water to form acetamide or with a bacterium to cause its death. Although the relatively resistant strain grows more slowly than the susceptible one and is killed less rapidly by metronidazole, the resistant strain displays the same relationship between the lethal action of metronidazole and metronidazole metabolism to acetamide. The relatively resistant strain, like the susceptible one, has an enhanced lethal response to metronidazole in the presence of a strain of Escherichia coli. The results suggest that the proposed labile reactive intermediate of metronidazole forms more slowly in the resistant strains.
Uptake, distribution, and anabolism of acyclovir in herpes simplex virus-infected mice
Authors: Biron K K , Noblin J E , de Miranda P , Elion G B
Published: June 2012

The uptake, distribution, and anabolism of the nucleoside analog 9-(2-hydroxyethoxymethyl) guanine (acyclovir) were compared in herpes simplex virus-infected and uninfected mice. Analyses of tissue distribution and the concentration of acyclovir after either a single dose or multiple doses failed to reveal significant differences between drug levels in infected and uninfected animals. Extracts of tissues from [8-14C] acyclovir-treated animals were examined by high-performance liquid chromatography to detect the presence of any phosphorylated forms of the drug. The sensitivity of this method did not allow a reproducible demonstration of acyclovir anabolism in herpes simplex virus-infected tissues owing to the low numbers of infected cells per organ.
Mice with persistent gastrointestinal Candida albicans as a model for antifungal therapy
Authors: Herrera C , Guentzel M N
Published: June 2012

Persistent infection of the gastrointestinal tract of CFW mice with Candida albicans was produced by the oral-intragastric inoculation of 6-day-old infants. Other intraabdominal organs (liver, kidneys, and spleen) were usually free of the organism in survivors at 20 days of age. However, all survivors retained high levels of the organism in the stomach and intestinal tract at 30 days of age. The possible utility of these persisting C. albicans infections of the gastrointestinal tract for the study of the efficacy of short-term antifungal therapy was studied. Drug treatment was initiated for a 2-week period when the survivors were 15 to 19 days old. Some representative antifungal agents in current use (i.e., amphotericin B, 5-fluorocytosine, and miconazole) effected significant reductions in the numbers of C. albicans in homogenates of gastrointestinal organs.
Inhibition of rotaviruses by selected antiviral substances: mechanisms of viral inhibition and in vivo activity
Authors: Smee D F , Sidwell R W , Clark S M , Barnett B B , Spendlove R S
Published: June 2012

Several RNA virus inhibitors were evaluated against simian (SA11) rotavirus infections in vitro and murine rotavirus gastroenteritis in vivo. Test compounds included 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin), 3-deazaguanine (3-DG), 3-deazauridine, and 9-(S)-(2,3-dihydroxypropyl)adenine [(S)-DHPA]. All drugs inhibited total infectious SA11 virus yields in MA-104 cells. Ribavirin, 3-DG, and (S)-DHPA affected [3H]uridine uptake into uninfected MA-104 cells in both the acid-soluble and -insoluble fractions. All drugs reduced the levels of dense (precursor) and light (complete) SA11 particle yields compared with control but did not alter the relative amounts of dense compared with light particles, suggesting that the agents did not interfere with virus assembly. Ribavirin and 3-DG inhibited SA11 polypeptide synthesis, as determined by polyacrylamide gel electrophoresis studies. None of the agents or mono- and triphosphate derivatives of ribavirin inhibited SA11 RNA polymerase activity. In murine rotavirus studies, oral therapy with ribavirin-2',3',5'-triacetate and (S)-DHPA increased mean survival time, but no increase in survivor rate was observed. 3-DG- and (S)-DHPA-treated mice had a more rapid weight gain than controls, suggesting a probable lessening of the severity of the disease.
Common R-plasmids in Staphylococcus aureus and Staphylococcus epidermidis during a nosocomial Staphylococcus aureus outbreak
Authors: Cohen M L , Wong E S , Falkow S
Published: June 2012

During a 7-month period in 1978 to 1979, 31 patients and personnel at a Kentucky hospital were colonized or infected with a Staphylococcus aureus strain resistant to clindamycin, erythromycin, gentamicin, methicillin, penicillin, and tetracycline. S. epidermidis with similar antibiotic resistance patterns had been isolated in this hospital in the year before the S. aureus outbreak. A 32-megadalton R-plasmid, pUW3626, mediating resistance to penicillin and gentamicin, was present in these isolates and in coisolated S. epidermidis from the same outbreak. By colony hybridization, pUW3626 was homologous to gentamicin R-plasmids from staphylococci isolated in other geographic areas. Our studies suggest that the emergency of antibiotic resistance in S. Aureus may result from genetic transfer from S. epidermidis as well as from the interhospital spread of resistant staphylococci.
Comparative trial of cefonicid and cefamandole in the therapy of community-acquired pneumonia
Authors: Wallace R J , Niefield S L , Waters S , Waters B , Awe R J , Wiss K , Martin R R , Greenberg S B
Published: June 2012

Cefonicid (Smith Kline & French Laboratories; D-75073) is a new parenteral cephalosporin with a markedly long half-life, high serum levels, and good in vitro activity against Haemophilus influenzae. Patients with community-acquired pneumonia were randomized 2:1 to receive cefonicid, 1 g daily (21 cases) or cefamandole, 1 g every 6 h (12 cases). The two groups were similar, except that the cefonicid patients were older (mean 42 versus 31 years). Peak serum levels of cefonicid averaged 133 microgram/ml after intravenous and 83 microgram/ml after intramuscular administration compared with 55 microgram/ml with intravenous cefamandole. All 9 patients on intramuscular cefonicid and 8 or 12 patients on intravenous cefonicid had trough serum levels of greater than 2.0 microgram/ml at 24 h. Sputum levels of cefonicid were usually between 2.0 and 4.0 microgram/ml and did not correlate with serum levels. Cefonicid was well tolerated, and all cefonicid patients responded clinically. Sputum cultures for H. influenzae or Streptococcus pneumoniae became negative in 6 of 7 cefamandole patients and 13 or 15 cefonicid patients. In in vitro studies, cefonicid inhibited 90% of beta-lactamase-negative h. influenzae at 0.5 microgram/ml and beta-lactamase-positive strains at 2.0 microgram/ml. Cefonicid inhibited 50% of S. pneumoniae at 1.6 microgram/ml, but required 6.4 microgram/ml to inhibit 90%. Cefonicid once a day appears to be as safe and as effective as cefamandole four times a day for therapy of community-acquired pneumonia.
Single-dose pharmacokinetics of ceftriaxone in infants and young children
Authors: Schaad U B , Stoeckel K
Published: June 2012

The pharmacokinetics of ceftriaxone were studied in five infants (7 to 15 months old) and five young children (24 to 70 months old). Both groups received a single 50-mg/kg dose in an intravenous infusion over 5 min. No major pharmacokinetic differences were observed between the two populations. The total (bound plus unbound) plasma concentration-versus-time data could be described in each case by a biexponential equation. Changes in renal clearance indicated time- and dose- dependent pharmacokinetic behavior. The fraction excreted unchanged in the urine (fu) and the biological half-life (t 1/2 (beta)) were, however, dose independent. The average values were 47% for fu (0 to 12 h) and 6.5 for T 1/2 (beta). Weight-corrected total systemic clearance was C1TS = 0.71 ml/min per kg; volume of distribution was VD (beta) = 394 mg/kg. The data support intravenous administration of 50 mg of ceftriaxone per kg of body weight every 12 h in assessing its activity against Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis in postneonatal-stage pediatric patients.
Alpha interferon administration to infants with congenital rubella
Authors: Arvin A M , Schmidt N J , Cantell K , Merigan T C
Published: June 2012

Three infants with congenital rubella syndrome were given human leukocyte (alpha) interferon at doses of 2 x 10(5) to 7 X 10(5) U/kg per day for 10 days. A transient decrease in pharyngeal virus excretion was observed with treatment. No significant side effects were associated with the administration of human leukocyte interferon to these infants.
Pharmacokinetics and bacteriological efficacy of cefoperazone, ceftriaxone, and moxalactam in experimental Streptococcus pneumoniae and Haemophilus influenzae meningitis
Authors: McCracken G H , Nelson J D , Grimm L
Published: June 2012

The pharmacokinetics and bacteriological efficacy of cefoperazone, cefuroxime, ceftriaxone, and moxalactam were evaluated in the experimental rabbit meningitis model of Haemophilus influenzae type b or Streptococcus pneumoniae infection. The cerebrospinal fluid penetration of these beta-lactam antibiotics was from 3 to 14% and was greater in Haemophilus-infected that in pneumococcus-infected animals. With the exception of moxalactam, the antibacterial activity in cerebrospinal fluid and change in concentration of bacteria during therapy with the test drugs were comparable to those of penicillin G in pneumococcal infection. In animals infected with H. influenzae, cefoperazone, moxalactam, and ceftriaxone were as effective as chloramphenicol in reducing the bacterial counts in cerebrospinal fluid. Moxalactam and ceftriaxone produced the largest cerebrospinal fluid bactericidal titers against this beta-lactamase-producing strain of Haemophilus. On the basis of these data, it was concluded that ceftriaxone and cefoperazone were effective against both pathogens in this meningitis model, whereas moxalactam was effective against only Haemophilus, and cefuroxime was effective against only S. pneumoniae.