bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative susceptibilities of Pseudomonas aeruginosa to 1-oxacephalosporin (LY 127935) and eight other antipseudomonal antimicrobial agents (old and new)
Authors: Yu V L , Vickers R M , Zuravleff J J
Published: June 2012

In vitro susceptibilities of 53 clinical isolates of Pseudomonas aeruginosa to nine antipseudomonal antibiotics were determined. From 96 to 100% of the isolates were susceptible to piperacillin, ticarcillin, and 1-oxacephalosporin (LY 127935). Of the aminoglycosides, 89, 82, 79, and 29% were susceptible to amikacin, tobramycin, gentamicin, and netilmicin, respectively. A total of 96% and 78% of the isolates were susceptible to 1-oxacephalosporin (LY127935) and cefotaxime, respectively, at concentrations of 62.5 micrograms/l. Supplementation of testing media by calcium and magnesium not only markedly increased the minimal inhibitory concentrations of the aminoglycosides, but also raised those of cefotaxime and the penicillins; no significant effect was noted with 1-oxace-phalosporin. Synergy was not demonstrated consistently in vitro with 1-oxace-phalosporin combined with either carbenicillin, ticarcillin, gentamicin, or tobramycin.
Mutational loss of sensitivity to mutacin GS-5 in Streptococcus pyogenes: characterization of a mutant deficient in receptor protein
Authors: Franker C K
Published: June 2012

By means of a stepwise selection procedure, mutants capable of growing in the presence of relatively high multiplicities of a bacteriocin from Streptococcus mutans GS-5 were obtained from a sensitivie strain of Streptococcus pyogenes. Mutacin-neutralizing activity of cell extracts containing receptor protein was examined in one variant that adsorbed 1/6 the amount of bacteriocin adsorbed by the parent strain under conditions equivalent to "saturation." Partially purified receptor protein from both parent and mutant cells neutralized an equivalent amount of bacteriocin on a weight-to-weight basis, indicating that in vitro there was no significant difference in affinity for the mutacin between the respective receptor fractions. Cell extracts from the mutant, solubilized by treatment with trichloroacetic acid, neither neutralized mutacin activity nor interfered with receptor protein-mediated mutacin neutralization in vitro. The mutant phenotype may thus represent a cell surface density of receptor protein which results in the adsorption of sublethal amounts of mutacin. The mutant retained its sensitivity to other mutacins, e.g., those produced by strains LM-7 and BHT of S. mutans, and did not differ from wild-type cells with respect to either detergent sensitivity (sodium lauryl sulfate and Triton X-100) or to inhibition by penicillin, rifampin, bacitracin, erythromycin, and tetracycline.
Pharmacokinetics of ceftizoxime in animals after parenteral dosing
Authors: Murakawa T , Sakamoto H , Fukada S , Nakamoto S , Hirose T , Itoh N , Nishida M
Published: June 2012

The pharmacokinetic profile of ceftizoxime was studied in mice, rats, dogs, and monkeys given the drug in a single parenteral dose. The serum data after an intravenous injection were analyzed by the two-compartment open model. Cefotiam, cefmetazole, cefotaxime, and cefamandole were used as reference drugs. High concentrations of ceftizoxime were attained in the sera of all test animals and in the tissues of rats after parenteral dosing. The serum concentrations of ceftizoxime were higher than those of the other antibiotics in large animals (dogs and monkeys), but were lower in small animals (mice and rats). About 80% of ceftizoxime was excreted unchanged in the 24-h urine of all species tested. The biliary excretion of ceftizoxime was low: 3.7% in rats and 0.59% in dogs. However, therapeutically significant concentrations of ceftizoxime were found in the bile of dogs. Ceftizoxime was stable in biological fluids such as serum, urine, and tissue homogenates, but cefotaxime was unstable in rat tissue homogenates. Binding of ceftizoxime to serum protein in all species was the lowest of all the antibiotics: 31% for humans, 17% for dogs, and 32% for rats.
In vitro and in vivo antibacterial activity of AB206, a new naphthyridine derivative
Authors: Nagate T , Kurashige S , Mitsuhashi S
Published: June 2012

AB206 (5,8-dihydro-5-methoxy-8-oxo-2H-1,3-dioxolo-4,5-g quinoline 7-carboxylic acid) is a novel antibacterial agent structurally related to nalidixic acid. AB206 has potent antibacterial activity against clinical isolates of gram-negative bacteria and is 4 to 18 times more active than nalidixic acid. AB206 inhibited the growth of Staphylococcus aureus and Pseudomonas aeruginosa, which were resistnat to nalidixic acid. Cross-resistance was not observed between AB206 and various antibiotics, and most bacterial strains resistant to nalidixic acid were susceptible to AB206. AB206 showed bactericidal activity against Escherichia coli, Proteus, Klebsiella pneumoniae, and P. aeruginosa. Chemotherapeutic effects after oral administration of AB206 in mice experimentally infected with E. coli, K. pneumoniae, and Proteus morganii showed that AB206 was two to four times more potent than nalidixic acid.
Pathogenicity in mice of strains of herpes simplex virus which are resistant to acyclovir in vitro and in vivo
Authors: Field H J , Darby G
Published: June 2012

Mice infected with three different isolates of herpes simplex virus (HSV) and treated with acyclovir (acycloguanosine; ACV) showed low levels of virus replication during the acute phase of infection. However, virus isolated from such treated mice did not show increased resistance to ACV. In contrast, resistant virus was readily isolated in vitro by passaging HSV in the presence of the drug. The degree of resistance was determined, in part, by the nature of the cells used to test the virus. The majority of ACV-resistant strains induced low or undetectable levels of HSV-specified thymidine kinase (TK), the enzyme responsible for phosphorylating ACV in infected cells. The TK-resistant strains were attenuated when injected into mice as indicated by reductions in virus replication, inflammation, and establishment of latent infections in sensory ganglia. The reduced virulence of the TK- strains was most marked after intracerebral inoculation, where the lethal dose was increased more than 100-fold compared with the parental isolates. However, one mutant is described which induced high levels of TK but was highly resistant to ACV and retained virulence for mice.
Antibiotic-resistant Staphylococcus epidermidis in patients undergoing cardiac surgery
Authors: Archer G L , Tenenbaum M J
Published: June 2012

Staphylococcus epidermidis isolates containing subpopulations resistant to 100 microgram of methicillin per ml were found on the chests of only 3 of 80 (4%) patients before cardiac surgery, whereas these highly resistant staphylococci were isolated from the chest wounds of 43 of 80 (54%) patients 5 days postoperatively. The percentage of patients colonized with methicillin-resistant S. epidermidis increased with time postoperatively. Methicillin-resistant postoperative isolates also contained organisms resistant to other antibiotics frequently used during these patients' hospitalizations. The percentages of patients with organisms resistant to various antibiotics were: nafcillin (100%), penicillin (100%), cephalothin (93%), cefamandole (80%), streptomycin (67%), and gentamicin (20%). Preoperative methicillin-susceptible isolates were generally susceptible to other antibiotics. Two patients with S. epidermidis prosthetic valve endocariditis caused by multiple antibiotic-resistant isolates were among the study patients. Antibiotic susceptibility patterns of each isolate from these two patients were identical to those of postoperative chest isolates from the same patient.
Antibiotic Therapy of Experimental
Staphylococcus epidermidis
Endocarditis
Authors: Vazquez Guillermo J. , Archer Gordon L.
Published: June 2012

Endocarditis was produced in rabbits with a methicillin-resistant
Staphylococcus epidermidis
isolate. Subpopulations resistant to other semisynthetic penicillins and cephalosporins were detected in the isolate. Their presence was probably responsible for the increase in minimum bactericidal concentrations and minimum inhibitory concentrations when tests with high inocula, rather than low inocula were pursued. Rabbits were treated for either 2 or 7 days with nafcillin, cephalothin, cefamandole, vancomycin, rifampin, or gentamicin. Spontaneous death was uncommon in either controls (84% survival) or treated animals (80 to 94% survival). There was no significant difference in the number of bacteria in vegetations of rabbits treated for 7 days with cephalothin, cefamandole, nafcillin, or no antibiotic (control). There was a significant reduction in total bacteria in vegetations of rabbits given vancomycin, gentamicin, or rifampin for 7 days as compared with cephalothin, cefamandole, nafcillin or control. Gentamicin or rifampin sterilized significantly more vegetations after 7 days than cephalothin, cefamandole, nafcillin, or control; rifampin was more effective in sterilizing vegetations than either gentamycin or vancomycin after 2 days. Mutants resistant to 10 μg of rifampin per ml comprised the total bacterial population cultured from vegetations of 2 of 17 rabbits treated with this antibiotic for 7 days; there was no change in the susceptibility of vegetation isolates to other antibiotics. Rifampin, vancomycin, or gentamicin may prove to be more effective in humans than cephalosporins or semisynthetic penicillins in the treatment of methicillin-resistant
S. epidermidis
endocarditis.
Incidence of R-plasmids in fecal flora of healthy household dogs
Authors: Hirsh D C , Ling G V , Ruby A L
Published: June 2012

Rectal swabs were taken from healthy household dogs that, insofar as could be determined, had not received antimicrobial drugs. Tetracycline-resistant coliforms comprised 80 to 100% of the total number of coliforms in 61 (65%) of the 94 dogs sampled. The median number of other resistance determinants possessed by these tetracycline-resistant coliforms was 5.1. Of the tetracycline-resistant strains studied, 97% were resistant to streptomycin; 76% were resistant to sulfonamides; 59% were resistant to ampicillin; 59% were resistant to kanamycin/neomycin; and 40% were resistant to chloramphenicol. A total of 64% of the strains was shown to transfer resistance by conjugation or by the aid of the sex factor F. Of the strains transferring resistance, 33% were found to transfer all of their resistance determinants.
Activity of cefotaxime-aminoglycoside combinations against aminoglycoside-resistant Pseudomonas
Authors: Murray P R
Published: June 2012

The activity of cefotaxime, either alone or combined with an aminoglycoside, was determined against 50 isolates of Pseudomonas aeruginosa, of which 50, 33, and 10 were resistant to gentamicin, tobramycin, and amikacin, respectively. Cefotaxime inhibited 34 isolates at a concentration of 16 microgram/ml and all isolates at 128 microgram/ml. The combinations of cefotaxime with gentamicin, tobramycin, and amikacin were synergistic against 30, 17, and 9 isolates, respectively, and no antagonism was observed with any combination. Synergism was obtained at clinically significant antibiotic concentrations for nine isolates with cefotaxime-gentamicin, five isolates with cefotaxime-tobramycin, and nine isolates with cefotaxime-amikacin.
Isolation of drug-resistant Aeromonas hydrophila from aquatic environments
Authors: McNicol L A , Aziz K M , Huq I , Kaper J B , Lockman H A , Remmers E F , Spira W M , Voll M J , Colwell R R
Published: June 2012

Antibiotic-resistant strains of Aeromonas hydrophila have been isolated from the natural environment in the Chesapeake Bay and areas surrounding Dacca and the Matlab region of Bangladesh. The Bangladesh strains carried resistance to chloramphenicol, streptomycin, and tetracycline, and 57% of them had a multiple streptomycin-tetracycline resistance phenotype correlated with the presence of a large plasmid. The Chesapeake Bay strains were resistant to polymyxin B ane tetracycline, but showed neither multiple resistance nor R-factor carriage. Twenty-five percent of the environmental strains were toxigenic in a Y-1 adrenal cell assay. Toxigenicity showed no positive correlation with drug resistance or with plasmid carriage. Environmental areas of heavy human impact appear to be associated with a higher incidence of antibiotic-resistant strains of aeromonads.
Combined effect of amphotericin B and rifampin on Candida species
Authors: Edwards J E , Morrison J , Henderson D K , Montgomerie J Z
Published: June 2012

Synergism with the combination of rifampin and amphotericin B in vitro has been demonstrated with a limited number of Candida strains. To extend these studies (particularly at clinically achievable levels of rifampin), we evaluated the in vitro combined activity of serial twofold dilutions of amphotericin B (0.1 to 6.0 microgram/ml) against 11 concentrations of rifampin (0.2 to 200 microgram/ml) for 40 strains of Candida: 20 Candida albicans, 7 Candida parapsilosis, 8 Candida tropicalis, 2 Candida stellatoidea, 2 Candida guilliermondii, and 1 Candida krusei by using a modified checkerboard microtitration technique. An additive or synergistic effect was seen for 45% of strains with 6.25 microgram of rifampin per ml added to amphotericin B. Whereas the minimal inhibitory concentration to amphotericin B alone was 0.4 microgram/ml or less for 50% of the strains, the percentage increased to 90 with the addition of 6.25 microgram of rifampin per ml. A similar effect was seen with killing: 25% of the strains were killed by 0.4 microgram or less of amphotericin B alone per ml, and 75% of the strains were killed with the addition of 6.25 microgram of rifampin per ml. In vivo studies are needed for confirmation of the usefulness of combined amphotericin B and rifampin therapy.
Comparison of cefoperazone, cefotaxime, and moxalactam (LY127935) against aerobic gram-negative bacilli
Authors: Lang S D , Edwards D J , Durack D T
Published: June 2012

This study compares the minimum inhibitory concentrations of cefoperazone, cefotaxime, and moxalactam (LY127935) for 446 aerobic gram-negative bacillary isolates and further compares the minimum inhibitory concentrations of LY127935 and these third-generation cephalosporins with those of thienamycin for Pseudomonas aeruginosa. Each antibiotic at low concentrations inhibited nearly all Enterobacteriaceae tested. Minimum inhibitory concentrations for P. aeruginosa were higher, but for a majority of strains they fell below achievable serum levels. Thienamycin and cefoperazone showed significantly greater antipseudomonal activity than did cefotaxime or LY127935. Cefoxitin-inducible resistance to LY127935 and the two cephalosporins was demonstrated among Enterobacter species but did not occur with thienamycin.
Mezlocillin Pharmacokinetics After Single Intravenous Doses to Patients with Varying Degrees of Renal Function
Authors: Frimodt-Möller Niels , Maigaard Sven , Toothaker Roger D. , Bundtzen Robert W. , Brodey Mitchell V. , Craig William A. , Welling Peter G. , Madsen Paul O.
Published: June 2012

The pharmacokinetics of mezlocillin were examined after single 2- and 4-g intravenous injections to three groups of male patients with creatinine clearances of I ≥ 60, II = 21 to 59, and III ≤ 20 ml min
−1
1.73 m
−2
. The decline in serum antibiotic levels was biphasic in all groups, and serum data were interpreted in terms of the pharmacokinetic two-compartment model. The mean elimination half-life of mezlocillin after the 2-g dose was 1.3, 1.5, and 2.3 h in groups I, II, and III, respectively. Equivalent values after the 4-g dose were 1.2, 1.6, and 4.4 h. In three functionally anephric patients the mean serum half-life of mezlocillin was 1.5 h during hemodialysis. Mean antibiotic levels in serum were greater than 10 μg ml
−1
for 4 h after the 2- and 4-g doses in group I and 8 h in group II. In group III, levels greater than 10 μg ml
−1
were maintained for 6 h after the 2-g dose and over 12 h after the 4-g dose. Mezlocillin distribution characteristics were largely independent of renal function and dose size. The only observable change occurred in the value of

V
dss

, which was significantly increased to 0.32 with 0.38 liter kg
−1
in severe renal impairment, compared to ca. 0.2 liter kg
−1
in subjects with normal or slightly impaired renal function. Cumulative 24-h urinary excretion accounted for 50, 40, and 3.2% of the dose in groups I, II, and III, respectively. Urine levels of mezlocillin were uniformly greater than the minimum inhibitory concentration for susceptible organisms for 12 h after dosing in all patients who produced urine. Because of the relatively small increase in the mezlocillin elimination half-life with declining renal function, dose reduction is necessary only in cases of severe renal impairment.
Antimicrobial susceptibility of Aeromonas hydrophila
Authors: Overman T L
Published: June 2012

Minimal inhibitory concentration determinations and disk diffusion and Autobac 1 susceptibility tests were performed on 22 strains of Aeromonas hydrophila. Eleven of the strains had discrepancies between Autobac and disk diffusion or minimal inhibitory concentration results. These discrepancies occurred with the beta-lactam antibiotics, primarily carbenicillin and cephalothin. It is recommended that any strain of A. hydrophila found to be susceptible to any of the beta-lactam antibiotics by using Autobac 1 should be retested by a disk diffusion or minimal inhibitory concentration method.
Effects of carbon sources on chemical composition of cell envelopes of Pseudomonas aeruginosa in association with polymyxin resistance
Authors: Gilleland H E , Conrad R S
Published: June 2012

Cells of Pseudomonas aeruginosa 015 were grown in basal medium with isobutyrate, DL-2-methylbutyrate, isovalerate, L-valine, L-isoleucine, L-leucine, D-glucose, or L-glutamate as the carbon source. Their resultant susceptibility to polymyxin B varied from a minimal inhibitory concentration of 2 U of polymyxin per ml for isobutyrate-grown cells to 975 U/ml for L-glutamate-grown cells. Cell envelopes from cells grown with each carbon source were compared with cell envelopes from cells grown in Mueller-Hinton broth as to their content of total protein, carbohydrate, and 2-keto-3-deoxyoctonate and as to their protein composition as determined by slab polyacrylamide gel electrophoresis. No pattern of cell envelope content of total protein, carbohydrate, 2-keto-3-deoxyoctonate, or outer membrane protein concentrations could be correlated with the degree of resistance to polymyxin. In these cells increased resistance to polymyxin was not associated with the loss of outer membrane proteins and lipopolysaccharide by the cell envelope.
In vitro susceptibility of Clostridium difficile isolates from patients with antibiotic-associated diarrhea or colitis
Authors: Dzink J , Bartlett J G
Published: June 2012

In vitro susceptibility tests were performed on 84 strains of Clostridium difficile to 11 antimicrobial agents. All isolates were from the stools of patients with antibiotic-associated diarrhea or colitis in which there was a cytopathic toxin that was neutralized by Clostridium sordellii antitoxin. Over 95% of the strains were susceptible to vancomycin, penicillin G, ampicillin, and metronidazole at concentrations of 4 microgram/ml. Susceptibility to clindamycin was variable; 60% of the strains were susceptible at 1 microgram/ml, and 9% were resistant at 128 microgram/ml. Studies of individual isolates showed that a major portion of the strains were relatively susceptible to the antimicrobial agent implicated in causing the disease.
Prospective, randomized trial of netilmicin and amikacin, with emphasis on eighth-nerve toxicity
Authors: Barza M , Lauermann M W , Tally F P , Gorbach S L
Published: June 2012

The toxicity of netilmicin was compared with that of amikacin in a randomized, prospective trial in 90 adults with a variety of serious gram-negative infections. There was no instance of antibiotic-related nephrotoxicity in the group given amikacin and only one instance in the group given netilmicin. Cochlear toxicity, as measured by a change in audiogram, occurred in 4/14 (28.5%) of the amikacin recipients and 3/19 (15.8%) of the netilmicin recipients. Vestibular toxicity, as determined by a change in ice-water calorics, was noted in 3/16 (19%) of the amikacin-treated patients and 0/15 of the netilmicin-treated individuals. Despite the trend toward lesser ototoxicity with netilmicin, the differences between the drugs were not statistically significant. There was, however, a significant association between male sex and the development of ototoxicity. Although many patients could not be evaluated for efficacy, there did not appear to be any difference in the therapeutic activity of the two drugs.
Events leading to cell death and lysis of Neisseria meningitidis in low concentrations of penicillin G
Authors: Neirinck L G , DeVoe I W , Ingram J M
Published: June 2012

Neisseria meningitidis SD1C exhibited a low tolerance to penicillin G (0.03 microgram/ml). Loss of viability in the absence of polyvinylpyrrolidone-40 and horse serum was independent of the concentration of antibiotic above the minimum inhibitory concentration, whereas the rate of bacteriolysis was concentration dependent. Penicillin-induced lysis was a secondary event in this organism. At low levels of penicillin G, growth characteristics, i.e., absorbancy changes, respiratory rate, and uptake of Mg2+, appeared normal during the first 90 min in penicillin; however, viability dropped dramatically. Additionally, total cell numbers remained constant while cell mass continued to increase at a rate normal for the population. The increase in cellular mass in the absence of cell division could be observed microscopically. Only one ultrastructural change induced by penicillin correlated with the loss in viability: the loss in continuity of the outer membrane with the peptidoglycan but only at the site of septum formation. This lesion did not occur when cells were grown in media supplemented with the protective agents polyvinylpyrrolidone-40 and horse serum. Under these conditions of growth and with relatively high levels of penicillin, constant viability was maintained, but cell division no longer occurred. Cell populations treated with penicillin in the presence of the protective agents became increasingly more dependent on the presence of these agents for total viability even in the absence of penicillin in the culture.
Antimycotic susceptibility testing of dermatophytes in microcultures with a standardized fragmented mycelial inoculum
Authors: Granade T C , Artis W M
Published: June 2012

Standardization of a fragmented dermatophyte mycelial inoculum free of conidia for use in a broth microculture antimycotic susceptibility testing system is described. Ten clinical dermatophyte isolates were grown in submerged broth cultures at 35 degrees C. The mycelia were harvested before conidia appeared and were fragmented to 10 to 50-micron segments with a Broeck ground-glass tissue grinder. The density of the fragmented mycelium preparation was found to be adjustable on the basis of its spectrophotometric density expressed as absorbance measured at 450 nm. The minimal absorbance density that produced a 100% inoculation efficiency was determined for each isolate, and from these data an absorbance density of 0.600 was selected for inoculation of microcultures used in antimycotic susceptibility testing. The 0.600-absorbance inoculum of each dermatophyte isolate was tested for its capacity to successfully inoculate antimycotic agent-containing microcultures and generate minimal inhibitory concentrations of griseofulvin, clotrimazole, miconazole, and ketoconazole. The effect of the length of incubation on the minimal inhibitory concentrations was determined. It was concluded that the 0.600-absorbance density fragmented mycelial inoculum assured the rapid and uniform inoculation of the broth microculture antimycotic susceptibility system.
Activity of beta-lactamase produced by Bacteroides fragilis against newly introduced cephalosporins
Authors: Sato K , Inoue M , Mitsuhashi S
Published: June 2012

The purified beta-lactamase from Bacteroides fragilis hydrolyzed newly introduced cephalosporins including cefuroxime and HR 756, and was inhibited by 7 alpha-methoxylated cephalosporins such as 6059-S and YM09330.
Mode of action of a new nalidixic acid derivative, AB206
Authors: Nagate T , Komatsu T , Izawa A , Ohmura S , Namiki S , Mitsuhashi S
Published: June 2012

A new chemotherapeutic agent, AB206, shows potent antibacterial activity against gram-negative bacteria, including most of the nalidixic acid-resistant strains tested. It strongly inhibits deoxyribonucleic acid (DNA) synthesis in Escherichia coli, but only slightly inhibits ribonucleic acid and protein synthesis. Its activity on DNA synthesis in vivo and in vitro is greater than that of nalidixic acid. AB206 also strongly inhibits in vivo DNA synthesis in nalidixic acid-susceptible and -resistant clinical isolates of Proteus and Serratia. AB206 shows high penetrability into E. coli cells, as demonstrated by antibacterial activity with or without ethylenediaminetetraacetic acid, inhibition of in vivo and in vitro DNA synthesis, and uptake of the drug into cells, as compared to nalidixic acid. It appears that the high antibacterial activity of AB206 may be explained both by its potent inhibitory action against DNA synthesis and also by its high penetrability into bacterial cells.
GR-20263: a new aminothiazolyl cephalosporin with high activity against Pseudomonas and Enterobacteriaceae
Authors: Verbist L , Verhaegen J
Published: June 2012

The in vitro activity of GR-20263, a new aminothiazolyl cephalosporin, was compared with the activities of other beta-lactam antibiotics by using 800 clinical bacterial isolates. GR-20263 was highly active (inhibition of 90% of the isolates between 0.03 and 1 microgram/ml) against the common Enterobacteriaceae and 5 to 20 times more active than cefuroxime, cefoxitin, and cephalothin. GR-20263 was three to six times less active than cefotaxime against Escherichia coli, Klebsiella pneumoniae, Salmonella, and Shigella, but three to four times more active than cefotaxime against Proteus vulgaris and Serratia marcescens. The activity of GR-20263 against Pseudomonas aeruginosa (with minimal inhibitory concentrations of 2 and 8 micrograms/ml for 90 and 100% of the isolates, respectively) was similar to that of tobramycin, 2 times that of cefsulodin, 5 times that of piperacillin, and 10 times that of cefotaxime. Against Haemophilus influenzae GR-20263 was three time more active than ampicillin. The beta-lactamase-producing strains were as susceptible to GR-20263 as the beta-lactamase-negative strains. GR-20263 was less active than cefotaxime and ampicillin against Staphylococcus aureus.
Activity of Ten Cephalosporins on Biomass of Methicillin-Susceptible and -Resistant
Staphylococcus aureus
Authors: Yourassowsky E. , Van Der Linden M. P. , Lismont M. J. , Crokaert F.
Published: June 2012

The growth curves automatically recorded and printed during the action of 10 cephalosporins on methicillin-susceptible and methicillin-resistant
Staphylococcus aureus
showed the following. (i) The biomass of methicillin-susceptible
S. aureus
exposed to the cephalosporins increased before lysis occurred (inoculum, 10
6
colony-forming units per ml). Lysis was more rapid with cephalothin and cephaloridine, whose minimal inhibitory concentrations were lowest. (ii) The same biomass increase followed by lysis occurred with methicillin-resistant
S. aureus
, and the speed of lysis was not different from those of cephalothin (without any regrowth), cefoxitin (with regrowth of a few strains), and cephaloridine (regrowth of all strains), with methicillin-susceptible strains. A 2-log increase of inoculum (10
8
colony-forming units per ml) did not modify significantly the speed of lysis with cephalothin, cephaloridine, and cefoxitin, but regrowth sometimes occurred. The early transitory lysis caused by cephaloridine, cephalothin, cefamandole, and cefoxitin was not suppressed by preincubation with 32 μg of methicillin per ml, but regrowth occurred more frequently. No lysis could be observed with cefazolin, cefotaxime, cephalexin, cephradine, cefuroxime, and cefaclor unless high concentrations were achieved. (iii) From a practical point of view, the early response of the growth curve (4 h) could not determine in every case whether a strain of
S. aureus
was resistant or susceptible to cephalosporin. A further study of the growth curve (18 of 24 h) was necessary for this purpose. Results obtained after a few hours with automated systems should be interpreted with great caution.
Comparison of moxalactam (LY127935) and cefotaxime against anaerobic bacteria
Authors: Jorgensen J H , Crawford S A , Alexander G A
Published: June 2012

The in vitro activities of moxalactam (LY127935 [6059S]) and cefotaxime were compared with those of cefoxitin, cefamandole, cefuroxime, carbenicillin, and penicillin by agar dilution susceptibility testing of a variety of anaerobic bacteria. Moxalactam proved to be the most active agent tested against Bacteroides fragilis and other species of the B. fragilis group. Moxalactam and cefotaxime showed activity similar to the other drugs against the remaining species of Bacteroides, Fusobacterium, Actinomyces, Propionibacterium, and Veillonella. Penicillin was the most effective drug tested against most species of Clostridium, the anaerobic gram-positive cocci, and Eubacterium lentum.
Hydrolysis of Cefotaxime by a beta-lactamase from Bacteroides fragilis
Authors: Pechère J C , Guay R , Dubois J , Letarte R
Published: June 2012

A beta-lactamase isolated from a strain of Bacteroides fragilis subsp. fragilis possessed hydrolytic activity toward cefotaxime. This antibiotic was degraded to a lower extent than was cephalothin, cephaloridine, and cefamandole, whereas cefoxitin remained unaffected by the enzyme. Kinetic parameters Vmax and Km for cefotaxime were calculated at 0.172 mumol/min and 1.1 X 10(-2) mM, respectively.
Therapy of obstetrical infections with moxalactam
Authors: Gibbs R S , Blanco J D , Castaneda Y S , St Clair P J
Published: June 2012

We evaluated moxalactam in 62 patients with puerperal or postabortal genital infections. In all patients, the initial dose was 6 g/day. In 84% of patients, we found anaerobes in genital specimens. Of aerobic isolates, only enterococci were resistant. Among anaerobes tested, only two isolates (a Clostridium leptum and a Bacteroides disiens) had minimal inhibitory concentrations of greater than or equal to microgram/ml. Good clinical responses occurred in 56 of 62 (90%). Moxalactam was well tolerated with little local irritation and minimal hepatic, renal, or hematological abnormalities.
Mezlocillin for treatment of infections in cancer patients
Authors: Issell B F , Bodey G P
Published: June 2012

Mezlocillin, at a dose of 3 g intravenously over a 2-h period every 4 h, was used for the treatment of 92 episodes of documented infections in 75 myelosuppressed cancer patients. The response rate in 59 evaluable bacterial infections was 46%. Eight of 23 patients with septicemia (35%) responded. The response rates for Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, the three most common gram-negative infections, were 42, 64, and 70%, respectively. Mezlocillin was well tolerated; the only toxicity attributable to this antibiotic was a skin rash in one patient. The formation of a false-positive urine protein reaction by mezlocillin was noted. This study demonstrated that mezlocillin administered as a single agent was effective against some infections in myelosuppressed cancer patients. The response rate for Klebsiella sp. infections was especially encouraging. However, because it had limited or little activity against many infections, especially those caused by P. aeruginosa and Staphylococcus aureus, the general use of mezlocillin as a single agent for treatment of infections in immunocompromised cancer patients cannot be recommended.
Inhibition of herpes simplex virus multiplication by the pokeweed antiviral protein
Authors: Aron G M , Irvin J D
Published: June 2012

The pokeweed antiviral protein inhibited the multiplication of herpes simplex virus type 1 in cell culture. The extent of antiviral activity was proportional to the length of time that the antiviral protein was present postinfection. The results demonstrate that the continued presence of the pokeweed antiviral protein is necessary for the maximum inhibition of virus yields.
In vitro and in vivo effects of the antimycotic drug ketoconazole on sterol synthesis
Authors: Van den Bossche H , Willemsens G , Cools W , Cornelissen F , Lauwers W F , van Cutsem J M
Published: June 2012

Ketoconazole, an orally active antimycotic drug, is a potent inhibitor of ergosterol biosynthesis in Candida albicans when added to culture media which support yeast or mycelial growth or to cultures containing outgrown mycelium. This inhibition coincides with accumulation of sterols with a methyl group at C-14 and can thus be attributed to an interference with one of the reactions involved in the removal of the 14 alpha-methyl group of lanosterol. When administered to rats infected with C. albicans, ketocanazole also inhibits fungal synthesis of ergosterol. A six-times-higher dose is required to effect cholesterol synthesis by rat liver.
Susceptibility of Bacterium actinomycetem comitans to 45 antibiotics
Authors: Höffler U , Niederau W , Pulverer G
Published: June 2012

The minimal inhibitory concentrations of 45 antimicrobial agents were determined for 14 strains of Bacterium actinomycetem comitans (Actinobacillus actinomycetem-comitans). All the strains showed good susceptibility to tetracyclines and chloramphenicol, but not to lincomycins. Some strains were clearly resistant to penicillins, cephalosporins, and nitroimidazoles. The lowest minimum inhibitory concentrations were observed with tetracycline, rolitetracycline, methacycline, minocycline, chloramphenicol, and cotrimoxazole.
Type II interferon induction and passive transfer depress the murine cytochrome P-450 drug metabolism system
Authors: Sonnenfeld G , Harned C L , Thaniyavarn S , Huff T , Mandel A D , Nerland D E
Published: June 2012

Induction of type II interferon by sensitization of mice with Mycobacterium tuberculosis strain BCG and challenge with tuberculin resulted in a depression of the cytochrome P-450 drug metabolism system of the liver. The degree of depression was significantly greater than in mice that were only sensitized to BCG. Cytochrome b5 levels were not affected. In addition, the level of the depression of the cytochrome P-450 system correlated with the levels of type II interferon induced. Passive transfer of exogenous type II interferon preparations also significantly depressed the cytochrome P-450 system. Passive transfer of mock interferon or of normal serum had no effect.
MK0787 (N-formimidoyl thienamycin): evaluation of in vitro and in vivo activities
Authors: Kropp H , Sundelof J G , Kahan J S , Kahan F M , Birnbaum J
Published: June 2012

The practical application of thienamycin, a novel beta-lactam antibiotic with a broad activity spectrum, was compromised by problems of instability. MK0787, N-formimidoyl thienamycin, does not have this liability. As reported, bacterial species resistant to most beta-lactam antibiotics, such as Pseudomonas aeurginosa, Serratis, Enterobacter, Enterococcus, and Bacteroides spp., are uniformly susceptible to MK0787, usually at one-half the inhibitory level of thienamycin. Bactericidal activity usually occurs at the minimal inhibitory concentration endpoint. Activity was reduced only at the highest inoculum densities tested and by a lessor factor than was observed with reference beta-lactam antibiotic active against P. aeruginosa and beta-lactamase-bearing strains. MK0787 exhibits a broad spectrum of in vivo activity when evaluated parenterally for efficacy against systemic infections in mice. The order of potency in vivo, 0.03 to 0.06 mg/kg for gram-positive species and 0.65 to 3.8 mg/kg for gram-negative infections including Pseudomonas, exceeded that of thienamycin and was at least 10-fold superior to reference beta-lactam antibiotics including two recently developed agents with antipseudomonal activity, cefotaxime and LY127935.
Susceptibility of Clostridium botulinum to thirteen antimicrobial agents
Authors: Swenson J M , Thornsberry C , McCroskey L M , Hatheway C L , Dowell V R
Published: June 2012

A total of 224 strains of Clostridium botulinum (including isolates from 14 patients with infant botulism and 4 with wound botulism) and 15 strains of C. sporogenes were tested by agar dilution for susceptibility to tetracycline, metronidazole, erythromycin, penicillin, rifampin, chloramphenicol, clindamycin, cephalothin, cefoxitin, vancomycin, sulfamethoxazole-trimethoprim, nalidixic acid, and gentamicin. At least 90% of the C. botulinum strains tested (except for nonproteolytic strains of toxin type F with penicillin) were susceptible to all drugs except sulfamethoxazole-trimethoprim, nalidixic acid, and gentamicin. Minimal inhibitory concentrations for strains from patients with infant and wound botulism were similar to those for other C. botulinum strains.
Penicillin-binding proteins in bacteria
Authors: Georgopapadakou N H , Liu F Y
Published: June 2012

The penicilllin-binding proteins (PBPs) of several gram-positive and gram-negative bacteria have been examined. The results indicate that: (i) PBPs are membrane proteins with molecular weights ranging from 40,000 to 120,000. When extracted with Triton X-100 from sonicated cells, they appear to fall into two patterns: one found in rods and the other in spheres. A major difference is in the low-molecular-weight component, which is usually the major PBP in bacilli but a minor one in cocci. (ii) There is a wide variation in both the number and the amount of PBPs in different bacteria, and taxonomically related bacteria tend to have similar PBP patterns. These patterns often correlate with the affinity of PBPs for penicillin and other beta-lactam antibiotics. (iii) The low-molecular-weight component usually releases penicillin spontaneously with a half-life of 10 min or less. Most, but not all, PBPs release bound penicillin in the presence of neutral hydroxylamine (0.2 to 0.8 M).
Incidence of polyene-resistant yeasts recovered from clinical specimens
Authors: Dick J D , Merz W G , Saral R
Published: June 2012

The development of resistance to amphotericin B and nystatin in yeast isolates was determined. Organisms recovered from patients on the oncology service, undergoing extensive chemotherapy for acute leukemia and bone marrow transplantation, were compared with yeasts recovered from patients on other services in the same hospital over a 7-month period. An agar dilution method was used to assay the susceptibility for each antibiotic; resistance was defined as a minimal inhibitory concentration of greater than or equal to 2 micrograms/ml for amphotericin B and greater than or equal to 16 micrograms/ml for nystatin. None of 625 isolates from 238 patients on non-oncology services demonstrated polyene resistance. Resistance only occurred in a subpopulation of oncology patients, in which 55 isolates (7.4%) from six patients (8.6%) exhibited polyene resistance. Resistance yeasts included Candida albicans (three strains), Candida tropicalis (one strain), and Torulopsis glabrata (two strains). All of the patients from whom resistant yeasts were recovered had experienced extensive chemotherapy with cytotoxic agents, granulocytopenia, and long-term treatment with both antibacterial and polyene antibiotics. Resistance to 2 micrograms of amphotericin B per ml and to 16 micrograms of nystatin per ml was associated with loss or marked depression of ergosterol in the cell membrane as measured by ultraviolet spectra. A significant incidence of polyene resistance in an oncology subpopulation was documented, suggesting a need for susceptibility testing in patients who are at high risk for development of drug-resistant fungal pathogens.
Radiometric prescreen for antitumor activity with Saccharomyces cerevisiae mutant strain
Authors: Speedie M K , Fique D V , Blomster R N
Published: June 2012

After modification, a technique for radiometrically measuring bacterial growth has been applied to a mutant strain of Saccharomyces cerevisiae. The assay is based on inhibition of 14CO2 release from [14C]glucose, which provides an extremely sensitive measure of cellular respiratory activity and growth. The criterion for antitumor activity is the differential inhibition of wild-type and mutant (distorted cell membrane) strains of the yeast. The system was optimized for medium, time of incubation, temperature, and size of inoculum. Known antitumor agents, including bleomycin, actinomycin D, adriamycin, and ellipticine were tested in the system, and differential inhibition was observed. Vincristine showed no inhibitory effects at the concentrations tried. The sensitivity for 20% inhibition ranged from 0.8 micrograms of adriamycin per ml to 0.14 mg of ellipticine per ml. Antifungal agents such as amphotericin B exhibited no differential inhibition. Antibacterial agents were inactive. This method may provide a rapid, sensitive, in vitro quantitative assay for antitumor agents which could be applied to a variety of assay needs and which can be run with facilities and equipment available in most laboratories.
Affinity of cefoperazone for penicillin-binding proteins
Authors: Matsubara N , Minami S , Matsuhashi M , Takaoka M , Mitsuhashi S
Published: June 2012

Cefoperazone (T-1551, CFP) a new semisynthetic cephalosporin, has a broad spectrum of antibacterial activity. We investigated the affinity of CFP to penicillin-binding proteins (PBPs) and the inhibition of peptidoglycan synthesis by CFP. CFP had high affinities for Escherichia coli PBP-3, -1Bs, -2, and -1A, in descending order, and low affinities for PBP-4, -5, and -6. Similarly, CFP showed high affinity for Pseudomonas aeruginosa PBP-3, -1A, -1B, -2, and -4, in descending order. It is known that E. coli PBP-3 and P. aeruginosa PBP-3 participate in cell division. These results are in good agreement with the formation of filamentous cells of E. coli and P. aeruginosa treated with CFP. CFP had lower inhibitory activities on D-alanine carboxypeptidase IA and IB of E. coli than that of penicillin G, but its inhibitory activities on the cross-link formation in peptidoglycan synthesis were the same as those of penicillin G and higher than those of ampicillin.
High-yield interferon induction by 10-carboxymethyl-9-acridanone in mice and hamsters
Authors: Taylor J L , Schoenherr C K , Grossberg S E
Published: June 2012

10-Carboxymethyl-9-acridanone (CMA) was shown to be a very potent interferon inducer in young and old Swiss albino as well as congenitally asplenic mice. This compound (molecular weight, 275) induced titers of interferon in plasma comparable to those obtained with the best viral inducers, attaining > 400,000 U/ml in mice in 2 to 3 h. CMA concentrations were highest in mouse plasma 1 h after intraperitoneal or oral delivery. Induction was dose dependent over a wide range. Intraperitoneal, subcutaneous, or intramuscular injections of CMA gave comparable ranges of interferon titers. Oral delivery by gavage gave lower titers (65,000 U/ml), but higher than those reported with other low-molecular-weight interferon inducers in mice. CMA injected into week-old hamsters (which usually produce iterferon poorly) induced levels of interferon as high as 6,400 U per ml of plasma in a dose-dependent fashion, but kinetics of interferon induction was less rapid than in mice. The mouse and hamster interferons induced by CMA had physical characteristics similar to those of virus-induced interferons of the homologous species. The unusually high yields of interferon obtainable with this chemical inducer suggest its use for further experimental antiviral or antitumor therapy.
Effect and mechanism of action of aphidicolin on yeast deoxyribonucleic acid polymerases
Authors: Plevani P , Badaracco G , Ginelli E , Sora S
Published: June 2012

The antibiotic aphidicolin inhibited in vitro deoxyribonucleic acid synthesis catalyzed by crude yeast extracts and by partially purified yeast deoxyribonucleic acid polymerases. The mechanism of action of aphidicolin on yeast deoxyribonucleic acid polymerase I was noncompetitive with deoxyguanosine 5'-triphosphate, deoxyadenosine 5'-triphosphate, and deoxythymidine 5'-triphosphate and was of the mixed type with deoxycytidine 5'-triphosphate. The relative ratio of enzyme to the template-initiator complex was important for detecting the inhibitory effect of the antibiotic. The inhibition of in vitro deoxyribonucleic acid synthesis by aphidicolin was reversible, and the effect on yeast deoxyribonucleic acid polymerase might have been partially mediated by some supplementary factor(s).
Penetration of beta-lactam antibiotics into their target enzymes in Pseudomonas aeruginosa: comparison of a highly sensitive mutant with its parent strain
Authors: Zimmermann W
Published: June 2012

Pseudomonas aeruginosa K 799/WT and a mutant of this strain, P. aeruginosa K 799/61 ("mutant 61"), that is very sensitive to most beta-lactam antibiotics tested were used to assess the importance of penetration barriers in the resistance of P. aeruginosa to penicillins and cephalosporins. The affinities of various beta-lactams to the penicillin-binding proteins found in membranes prepared from both strains were compared by measuring their competition for the binding of benzyl[14C] penicillin to each of these proteins. Only minor differences between the wild type and the mutant 61 were found. The high sensitivity of the mutant therefore cannot be attributed to drastic alterations of these target proteins, nor can the resistance of the wild type be ascribed to penicillin-binding proteins with low affinities for beta-lactams. Experiments in which the ease of penetration of beta-lactams into the penicillin-binding proteins was measured with exponentially growing intact cells instead of membranes, however, clearly demonstrated an easy access of beta-lactam antibiotics to these proteins in the mutant and an efficient exclusion from the same targets in the wild type.
Antifungal and antibacterial activities of diarylamidine derivatives
Authors: Anné J , De Clercq E , Eyssen H , Dann O
Published: June 2012

The antifungal and antibacterial properties of a series of 70 diarylamidine derivatives were evaluated. Several of these compounds exhibited considerable antimicrobial potency. A survey of the structure-activity relationship demonstrated that minor structural variations resulted in significant changes of antimicrobial activity. In general, the structural features required for antifungal activity coincided with those required for antibacterial activity. Both the antifungal and the antibacterial properties of the diarylamidines depended on the presence and the positions, of both amidino groups, on the nature of the central bridge connecting the two aryl moieties, and on the nature of these aryl residues (preferably indole). The most active compound was evaluated for its activity against Candida albicans infection in mice.