bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of orally administered probenecid on the pharmacokinetics of cefoxitin
Authors: Vlasses P H , Holbrook A M , Schrogie J J , Rogers J D , Ferguson R K , Abrams W B
Published: June 2012

To characterize the effect of orally administered probenecid on the pharmacokinetics of cefoxitin in healthy male volunteers, we administered to one group of six subjects 2 g of cefoxitin by intravenous (i.v.) bolus either alone, with 1 g of probenecid concomitantly, or when 1 g of probenecid was administered 1 h previously by using a crossover design. Likewise, we administered to a second group of six subjects 2 g of cefoxitin intramuscularly (i.m.) together with 1 and 2 g of probenecid. Probenecid increased the mean terminal half-life and the area under the serum cefoxitin concentration-time curve (AUC0-24) and decreased renal clearance, but did not alter the volume of the central compartment or the total urinary recovery of i.v.-administered cefoxitin; pretreatment with probenecid produced a greater increase in cefoxitin AUC0-24 and a constant decrease in renal clearance compared to concomitant probenecid. The AUC0-24 after i.m.-administered cefoxitin was greater after 2 g than 1 g of probenecid; the AUC0-24 after i.v.-and i.m.-administered cefoxitin was similar after 1 g of probenecid was given concomitantly. Cefoxitin AUC0-24 was increased further when 1 g of probenecid was given before i.v.-administered cefoxitin or when 2 g of probenecid was given with i.m.-administered cefoxitin. The effect of probenecid was related to both timing and dose.
Effect of fatty acids on action of polyene antibiotics
Authors: Iannitelli R C , Ikawa M
Published: June 2012

Fatty acids cause a decrease in the absorption spectra of the antifungal polyene macrolide antibiotics nystatin, filipin, candicidin, and amphotericin B. For nystatin, filipin, and candicidin, this decrease in absorption could be correlated with the activity of the fatty acids in protecting the yeast Saccharomyces cerevisiae against the action of these antibiotics. With amphotericin B a correlation was observed between the decrease in absorption caused by certain derivatives of fatty acids and the protective action of these derivatives against the activity of amphotericin B on yeast. It is concluded that, like the sterols, fatty acids also interact with the polyene antibiotics and thereby reduce their effective concentrations.
TEM-type beta-lactamase production in Haemophilus ducreyi
Authors: MacLean I W , Bowden G H , Albritton W L
Published: June 2012

A TnA-containing 6.0-megadalton plasmid (pJB1) isolated from Haemophilus ducreyi was shown to code for a beta-lactamase similar to the TEM-1-type beta-lactamase originating from the ampicillin transposon Tn2.
Antibacterial activities of a new stabilized thienamycin, N-formimidoyl thienamycin, in comparison with other antibiotics
Authors: Kesado T , Hashizume T , Asahi Y
Published: June 2012

The in vitro activity of a new crystalline derivative of thienamycin, N-formimidoyl thienamycin (MK0787), was tested against 46 laboratory reference strains and 2,158 clinical isolates of gram-positive and -negative bacteria, including anaerobes, and compared with cefoxitin, cefaxolin, carbenicillin, and amikacin. MK0787 was significantly more active than the reference antibiotics against most bacteria tests. MK0787 was 16- to 500-fold more active than the other antibiotics against Staphylococcus aureus, Streptococcus pneumoniae, and group A and group B streptococci, inhibiting most isolates at concentrations less than 0.031 micrograms/ml. The inhibition concentration against over 90% of 156 strains of Streptococcus faecalis was 1 micrograms/ml. MK0787 had slightly less activity than carbenicillin against Haemophilus influenzae. The minimal inhibitory concentrations of MK0787 against strains of Enterobacter spp., Citrobacter spp., Serratia marcescems. Pseudomonas aeruginosa, and Clostridium difficile that are resistant to currently available antibiotics were less than or equal to 4 micrograms/ml. The only species found resistant to MK0787 was Pseudomonas maltophilia, which was equally nonsusceptible to the other reference antibiotics.
In vitro activity of mecillinam against anaerobic bacteria
Authors: Steinkraus G E , McCarthy L R
Published: June 2012

A microtiter broth dilution method was employed to determine the in vitro activity of mecillinam against 201 recent clinical isolates of anaerobic bacteria. Both the anerobic gram-positive and anaerobic gram-negative bacilli displayed a wide range of minimal inhibitory concentrations of mecillinam; most strains were resistant to the antibiotic. The anaerobic cocci exhibited a narrower range of minimal inhibitory concentrations than were observed with other anaerobes, but also exhibited mecillinam resistance. As a single durg, mecillinam does not appear to be an effective antimicrobial agent against anaerobic bacteria.
Defective killing of enterococci: a common property of antimicrobial agents acting on the cell wall
Authors: Krogstad D J , Pargwette A R
Published: June 2012

We tested the ability of antimicrobial agents that act on the cell wall to kill enterococci and found defective killing (a minimal bactericidal concentration/minimal inhibitory concentration ratio of greater than or equal to 32) with both beta-lactams (penicillin G and cephalothin) and non-beta-lactams (vancomycin, cycloserine, and bacitracin). Our results indicate that the resistance of enterococci to antimicrobial killing spans the spectrum of agents known to inhibit cell wall synthesis and suggest that the mechanism responsible for enterococcal resistance to killing by these drugs may be a defective autolytic enzyme system.
In vitro antimicrobial activity of cefotaxime, a new cephalosporin
Authors: Masuyoshi S , Arai S , Miyamoto M , Mitsuhashi S
Published: June 2012

Cefotaxime, a new semisynthetic cephalosporin derivative, showed a broad spectrum of antibacterial activity against clinically isolated strains of gram-positive and gram-negative bacteria. This cephalosporin was slightly less active than cefazolin against Staphylococcus aureus but 4 to 300 times as active as carbenicillin against gram-negative organisms, including Pseudomonas aeruginosa, Pseudomonas cepacia, Enterobacter cloacae, and Serratia marcescens. Cefotaxime was the most active compound against members of the Enterobacteriaceae and 20- to 100-fold more active than cefoxitin against the indole-positive Proteus group. The minimal bactericidal concentrations of the compound were identical to, or two times higher than, the minimal inhibitory concentrations against Escherichia coli and P. aeruginosa and four times higher against S. marcescens. A reduction of inoculum size decreased greatly the minimal inhibitory and bactericidal concentrations of cefotaxime against E. coli P. aeruginosa, and S. marcescens. The antibiotic was very stable to penicillinase and cephalosporinase produced by gram-negative bacteria, including Proteus vulgaris.
Cefroxadine (CGP-9000), an orally active cephalosporin
Authors: Yasuda K , Kurashige S , Mitsuhashi S
Published: June 2012

Cefroxadine (GCP-9000; CXD), 7 beta[D-2-amino-2-(1,4-cyclohexadienyl)-acetamido]-3-methoxy-ceph-3-em-carboxylic acid, is a new orally active cephalosporin derivative. The spectrum of antibacterial activity of CXD is identical with that of cephalexin (CEX), but CXD was twofold more effective than CEX against Escherichia coli and Klebsiella pneumoniae, CXD was as stable to penicillinase as CEX, but it was hydrolyzed by cephalosporinase, with a relative rate of hydrolysis similar to that of CEX. The affinities of CXD and CEX to penicillin-binding proteins of E. coli were estimated; the affinity of CXD to penicillin-binding protein 1Bs was higher than that of CEX. Consistent with this, CXD had more intensive lytic activity than CEX. In vivo antibacterial activities of CXD and CEX were compared using systemic infections of mice with E. coli and K. pneumoniae; CXD was consistently more active than CEX.
Hypoxanthine-arabinoside pharmacokinetics after adenine arabinoside administration to a patient with renal failure
Authors: Aronoff G R , Szwed J J , Nelson R L , Marcus E L , Kleit S A
Published: June 2012

Hypoxanthine arabinoside pharmacokinetics were measured during an adenine arabinoside continuous intravenous infusion and during hemodialysis in a patient with renal failure. Therapeutic guidelines for adenine arabinoside in renal failure are provided based on an elimination half-life of 4.7 h and a plasma clearance of 87.9 ml/min for the hypoxanthine metabolite.
Absorption and excretion of miloxacin in mice, rats, and dogs
Authors: Izawa A , Yoshitake A , Komatsu T
Published: June 2012

Miloxacin, a synthetic antibacterial agent structurally related to oxolinic acid, has a broad spectrum of activity in vitro against gram-negative bacteria and considerable activity in vivo against infections with these bacteria. These observations led to studies on the absorption and excretion of miloxacin in mice, rats, and dogs after administration of a single oral dose. Studies on oxolinic acid have been included for comparison. Peak serum levels of miloxacin, attained 1 h after administration of 20, 50, and 100 mg/kg to rats and dogs, were approximately 20, 40, and 60 micrograms/ml, respectively. Peak levels in mice receiving the same dose were 15, 60, and 80 micrograms/ml at 0.5 h. Peak serum levels of oxolinic acid were attained 0.5 to 1 h later than the above times at comparable doses and were one-half to one-fourth those of miloxacin. Urinary recovery of miloxacin at the above doses ranged from 3.2 to 6.5% during the 24-h posttreatment period. Recoveries of oxolinic acid were one-half to one-fifth those of miloxacin. At a 50-mg/kg dose, rats excreted 4.6% of the miloxacin in bile in the 20-h posttreatment period.
Purification and properties of cephalosporinase in Escherichia coli
Authors: Minami S , Inoue M , Mitsuhashi S
Published: June 2012

Cephalosporin beta-lactamase (cephalosporinase) was purified from a strain of Escherichia coli resistant to beta-lactam antibiotics. The purified enzyme preparation gave a single protein band on polyacrylamide gel electrophoresis, and its molecular weight was 39,000 from sodium dodecyl sulfate-acrylamide gel electrophoresis. Its isoelectric point was 8.7. The specific activity was 31.7 mumol/min per mg of protein of the purified enzyme for the hydrolysis of cephaloridine. The optimal pH was about 8.0, and the optimal temperature was 36 degrees C. The enzyme activity was inhibited by iodine, some divalent metallic ions, semisynthetic penicillins, cefuroxime-type cephalosporins, and cephamycin derivatives. The enzymological properties of the purified preparation have been compared with those of beta-lactamases from other gram-negative bacteria.
Cefotaxime: in vitro activity and tentative interpretive standards for disk susceptibility testing
Authors: Fuchs P C , Barry A L , Thornsberry C , Jones R N , Gavan T L , Gerlach E H , Sommers H M
Published: June 2012

Tested against 9,412 recent clinical isolates, cefotaxime exhibited 8 to 64 times greater activity against the Enterobacteriaceae than did cephalothin and two to four times greater activity against Pseudomonas aeruginosa, but only one-half to one-eighth the activity of cephalothin against staphylococci. Using 420 different clinical isolates, but with comparable minimal inhibitory concentration (MIC) distributions, disk diffusion-MIC regression analyses were performed, using 5- and 30-micrograms cefotaxime disks. Cefotaxime MIC susceptible and resistant breakpoints of less than or equal to 8 and greater than 32 micrograms/ml are tentatively proposed. Based on the MIC breakpoints, the data showed the best discrimination among the three susceptibility categories (susceptible, indeterminate, and resistant) when the 30-micrograms cefotaxime disk was used. The zone diameter breakpoints as determined by the error rate-bounded method and regression analysis were greater than or equal to 23 mm for susceptible, 15 to 22 mm for indeterminate, and less than or equal to 14 mm for resistant.
Pharmacokinetics of Ro 13-9904, a broad-spectrum cephalosporin
Authors: Seddon M , Wise R , Gillett A P , Livingston R
Published: June 2012

The pharmacokinetics of the new cephalosporin Ro-13-9904 were studied in six healthy male volunteers receiving a 500-mg dose as a bolus intravenously. Tissue penetration of the antibiotic was estimated by using a cantharides blister method. The data obtained fitted a two-compartment open model. The mean elimination half-life was about 8 h, which is considerably longer than that of other beta-lactam compounds. The distribution volume was 4.3 liters in the central compartment. Levels of Ro 13-9904 in blister fluid exceeded those in serum after 6.5 h. Approximately 60% of the antibiotic was excreted in the urine.
In vitro antibacterial activity and susceptibility of the cephalosporin Ro 13-9904 to beta-lactamases
Authors: Shannon K , King A , Warren C , Phillips I
Published: June 2012

The in vitro activity of Ro 13-9904 was assessed against clinical isolated of common bacteria. Its activity against most enterobacteria was similar to that of cefotaxime and moxalactam, but it was even more active than these compounds against all Proteus species. It was also highly active against Haemophilus influenzae and Neisseria gonorrhoeae, including beta-lactamase producers. Like cefotaxime and moxalactam, Or 13-9904 was approximately eightfold more active than carbenicillin against most isolates of Pseudomonas aeruginosa and also active against highly carbenicillin-resistant isolates, but it was relatively inactive against moderately carbenicillin-resistant isolates. Ro 13-9904 also resembled cefotaxime and moxalactam in that it was active, though less so than cephaloridine, against staphylococci and streptococci, except for methicillin-resistant staphylococci and Streptococcus faecalis, which were resistant to it. It was less active than cefoxitin but slightly more active than ampicillin against both Bacteroides fragilis and other Bacteroides spp. Ro 13-9904 was resistant to most beta-lactamases but was attacked by enzymes from B. fragilis, isolates of indole-positive Proteus species, and also by a cefoxitin-hydrolyzing enzyme from an isolate of Enterobacter cloacae.
Activity of 2-acetylpyridine thiosemicarbazones against Trypanosoma rhodesiense in vitro
Authors: Casero R A , Klayman D L , Childs G E , Scovill J P , Desjardins R E
Published: June 2012

Twenty-seven 2-acetylpyridine thiosemicarbazones and analogs were tested for antitrypanosomal activity against Trypanosoma rhodesiense using a semiautomated in vitro assay system. Activity was determined by relative inhibition of uptake of two radiolabeled macromolecular precursors, [methyl-3H]thymidine and L-[U-14C]leucine, as compared to untreated controls. It was observed that the nitrogen atom of the pyridyl moiety of the 2-acetylpyridine thiosemicarbazones was essential for antitrypanosomal activity. The 2-acetylpyridine thiosemicarbazones generally inhibited the uptake of L-[U-14C]leucine to a greater extent than they inhibited [methyl-3H]thymidine uptake. Twenty-four of the 27 compounds tested exhibited activity comparable to that found for the antitrypanosomal agent ethidium bromide.
Comparison of cefotaxime and moxalactam pharmacokinetics and tissue levels
Authors: Wise R , Baker S , Livingston R
Published: June 2012

The pharmacokinetics of cefotaxime and moxalactam were compared in six healthy male volunteers aftr the administration of 1-g doses intravenously. Penetration of the compounds into tissue fluid was studied in cantharides-induced blisters. Both serum and tissue fluid levels of moxalactam were higher than those of cefotaxime. The elimination half-life of cefotaxime was 1.2 h, and that of moxalactam was 2.85 h. On the average, 50.5% of cefotaxime and 87.5% of moxalactam were recovered in the urine in 24 h.
Cephamycin C Treatment of Induced Enterotoxigenic Colibacillosis (Scours) in Calves and Piglets
Authors: Jacks Thomas M. , Schleim Klaus-Dieter , Judith Frederick R. , Miller Brinton M.
Published: June 2012

Cephamycin C is a β-lactam antibiotic that has broad gram-negative activity and is resistant to degradation by β-lactamases and safe for use in animals. In colostrum-fed calves infected with
Escherichia coli
strain B44, cephamycin C administered by gavage at 31.3 to 1,000 mg per calf (0.75 to 24 mg/kg) twice a day for 6 days starting at 20 h post-inoculation eliminated the diarrhea and reduced the mortality from 90% in infected, nonmedicated calves to 14% in infected, medicated calves (
P
< 0.01). Comparable results were obtained with a shorter treatment regimen (30 mg of cephamycin C per calf [0.71 mg/kg] twice a day for 3 days). In colostrum-fed piglets infected with
E. coli
strain P155 and housed in cages, cephamycin C administered prophylactically by gavage at 12.5 mg per piglet (10.4 mg/kg) twice a day for 4 days completely prevented both diarrhea and mortality, whereas nonmedicated piglets had 100% diarrhea and all died. When eight doses of cephamycin C were given therapeutically starting at 6 h post-inoculation, mortality was reduced from 79 to 23% (
P
< 0.02), and diarrhea was eliminated in the surviving medicated piglets by 4 days post-inoculation. In infected suckling piglets, cephamycin C administered therapeutically by gavage at 12.5 mg per piglet twice a day for 3 days starting at 6 h post-inoculation, diarrhea and mortality were reduced (
P
< 0.05): infected, nonmedicated piglets had 87% diarrhea and 75% mortality, whereas infected, medicated piglets had 25% diarrhea and 31% mortality. All surviving medicated piglets had solid feces by 2 days post-inoculation. Thus, cephamycin C was highly effective in restoring the calves and piglets to good health by eliminating diarrhea and reducing mortality.
In vitro susceptibility of gram-negative bacilli from pediatric patients to moxalactam, cefotaxime, Ro 13-9904, and other cephalosporins
Authors: Shelton S , Nelson J D , McCracken G H
Published: June 2012

Moxalactam, Ro 13-9904, cefotaxime, cefoperazone, older cephalosporins, and four aminoglycosides were tested in vitro against 432 strains of gram-negative bacteria isolated from pediatric patients. The new drugs were uniformly active against coliform bacilli obtained from patients with meningitis and against aminoglycoside-resistant coliform bacilli.
pJT2: unusual H1 plasmid in a highly virulent lactose-positive and chloramphenicol-resistant Salmonella typhimurium strain from calves
Authors: Timoney J F , Taylor D E , Shin S , McDonough P
Published: June 2012

A lactose-positive and chloramphenicol-resistant strain of Salmonella typhimurium of high virulence was isolated from an outbreak of enteric and septicemic salmonellosis in veal calves. the lactose-positive marker was located on an H1 plasmid, pJT2, together with resistance to chloramphenicol, streptomycin, sulfonamides, and tetracycline, pJT2 was unusually large and had a molecular weight of about 150 X 10(6). A similar plasmid was also present in a third of the Escherichia coli strains isolated from the intestines of septicemic calves during the outbreak. Spontaneously derived Lac- derivatives of pJT2 had an approximate molecular weight of 140 X 10(6).
Tetracycline transport in Bacteroides fragilis
Authors: Fayolle F , Privitera G , Sebald M
Published: June 2012

In susceptible strain of Bacteroides fragilis, tetracycline uptake is biphasic. The initial phase is independent of adenosine 5'-triphosphate synthesis, which is coupled to fumarate reduction; this phase is not altered by expression of tetracycline resistance genes in a resistant strain. The second phase appears to occur by active transport, since it is largely reduced by rotenone, an inhibitor of electron transport to fumarate; moreover, this phase is under negative control of the tetracycline resistance gene.
Enzymatic method for rapid and sensitive determination of beta-lactam antibiotics
Authors: Frère J M , Klein D , Ghuysen J M
Published: June 2012

A rapid and sensitive procedure for the estimation of beta-lactam antibiotics is described which makes use of the ability of these antibiotics to inactivate the R39 DD-carboxypeptidase. Depending on the values of the kinetic parameters which govern the reaction, the antibiotics fall into two groups. The lower limit for the quantitative estimation of the antibiotics of groups I and II is about 5 and 50 pmol/ml, respectively. The procedure has been adopted to biological fluids such as human sera and cows' milk.
Metabolic fate of SCE-1365, a new broad-spectrum cephalosporin, after parenteral administration to rats and dogs
Authors: Tanayama S , Yoshida K , Adachi K , Kondo T
Published: June 2012

Disposition of [14C]SCE-1365 was studied in rats and dogs after intramuscular or intravenous injection. The plasma level of [14C]SCE-1365 peaked at 15 min after intramuscular administration and declined rapidly to give half-lives of 27 and 39 min, respectively, in rats and dogs. After intravenous dosage, half-lives were 22 and 32 min, respectively, in rats and dogs. In both animals, the plasma levels of 14C were made up largely of unchanged antibiotic. Binding to plasma protein was 91 and 31%, respectively, in rats and dogs. Tissue levels of [14C]SCE-1365 administered intramuscularly to rats peaked at 15 min and were highest in the kidney and lowest in the brain, with plasma, liver, lung, heart, intestinal wall, and adrenal gland occupying intermediary positions in the order listed. The concentration of [14C]SCE-1365 in erythrocytes was very low, as was the level of the antibiotic in rat fetuses. The milk of rats given [14C]SCE-1365 intramuscularly contained detectable levels of 14C. [14C]SCE-1365 was completely eliminated from the bodies of rats and dogs within 24 to 48 h. In both animals, a large amount of the dosed 14C was excreted in urine as unaltered antibiotic. The remainder was eliminated in the feces via bile. In rats, [14C]SCE-1365 was eliminated by both glomerular filtration (33%) and tubular secretion (67%). An active transport process appeared to be involved in biliary excretion in rats.
Influence of chemical modification of N alpha-cocoyl-L-arginine ethyl ester on its hepatitis B surface antigen-inactivating effect
Authors: Sugimoto Y , Toyoshima S
Published: June 2012

We have reported previously that N alpha-cocoyl-L-arginine ethyl ester (CAE) strongly inactivates hepatitis B surface antigen (HBsAg; Sugimoto and Toyoshima, Antimicrob. Agents Chemother. 16:329--332, 1979). Replacement of the L-arginine moiety of CAE by L-lysine did not decrease the HBsAg-inactivating effect of CAE, whereas replacement by some neutral amino acids and L-ornithine decreased it. Esterification of the carboxyl group of N alpha-acyl-L-arginine enhanced its inactivating effect. When the ethyl ester of CAE was converted to an amide group, the effect was appreciably decreased. Modification of the carboxyl group was essential for the inactivation. The effectiveness of N alpha-acyl-L-arginine ethyl ester depends upon the length of the acyl group, with the optimum length for the inactivation of HBsAg being C12 to C14. In addition to CAE, N alpha-lauroyl-L-lysine ethyl ester and N alpha-cocoyl-L-arginine amide were found to be strong inactivators of HBsAg. Significant inactivating effects on HBsAg were not observed in many anionic detergents containing an amino acid. These results suggest that for strongly inactivating HBsAg, a compound should contain a special amino acid, such as L-arginine, and a long acyl group and exhibit a cationic property.
Klebsiella neonatal injections: mechanism of broadening aminoglycoside resistance
Authors: Hardy D J , Legeai R J , O'Callaghan R J
Published: June 2012

Kanamycin resistance in eight strains of Klebsiella pneumoniae isolated during an outbreak of infection in a neonatal intensive care unit was found to be transferable and mediated by neomycin phosphotransferase. After gentamicin was used to control infections caused by kanamycin-resistant organisms, a strain resistant to gentamicin emerged. Gentamicin resistance in this ninth strain was not transferable and was accompanied by resistance to tobramycin, amikacin, and streptomycin. Enzymatic modifications of aminoglycosides other than neomycin and kanamycin could not be demonstrated either by filter binding assays or by electrophoresis of a radioactive aminoglycoside substrate. The strain with broad aminoglycoside resistance contained six plasmid deoxyribonucleic acid bands, none of which appeared to be different in molecular weight from plasmid deoxyribonucleic acid bands in strains isolated before the institution of gentamicin therapy. The broadening of resistance was accompanied by reduced uptake of radioactively labeled streptomycin and gentamicin. The relationship between aminoglycoside resistance and reduced drug transport in the absence of any enzymatic modification is discussed.
In vitro evaluation of Ro 13-9904
Authors: Hinkle A M , Bodey G P
Published: June 2012

The in vitro activity of a new investigational cephalosporin, Ro 13-9904, was compared with those of four cephalosporins (cephalothin, cefamandole, cefoxitin, and moxalactam), five semisynthetic penicillins (mezlocillin, piperacillin, carbenicillin, ticarcillin, and azlocillin), and the aminoglycoside tobramycin. Ro 13-9904 inhibited 75% of all isolates of Enterobacteriaceae at a concentration of 6.25 micrograms/ml, including Enterobacter spp., Serratia marcescens, and indole-positive Proteus spp. Ro 13-9904 was only minimally active against Pseudomonas aeruginosa and enterococci. There was no significant change (greater than or equal to 2 dilutions) in drug activity when tested in various pH and media. A significant inoculum effect occurred when the size of the inoculum was increased from a concentration of 10(5) to 10(7) organisms per ml.
Erythro-9-(2-hydroxy-3-nonyl) Adenine alone and in combination with 9-beta-D-arabinofuranosyladenine in treatment of systemic herpesvirus infections in mice
Authors: Shannon W M , Arnett G , Schabel F M , North T W , Cohen S S
Published: June 2012

Although the antiviral activity of erythro-9-(2-hydroxy-3-nonyl)adenine, a potent adenosine deaminase inhibitor, against herpes simplex virus type 1 in cell culture was readily confirmed, the compound was found to be totally ineffective in the treatment of experimentally induced systemic herpes simplex virus type 1 infections in Swiss mice. Data were obtained, however, which clearly indicated that the antiviral potency of 9-beta-D-arabinofuranosyladenine in vivo could be enhanced by the co-administration of low, nontoxic doses of erythro-9-(2-hydroxy-3-nonyl)adenine.
Interpretive standards for disk susceptibility tests with Sch 21420 and amikacin
Authors: Barry A L , Thornsberry C , Jones R N , Gerlach E H
Published: June 2012

Disk susceptibility tests with two structurally related aminoglycosides (amikacin and Sch 21420) were evaluated. Tests with 10- and 30-micrograms amikacin disks confirmed previous recommendations for interpretive zone standards; 30-micrograms disks are preferred. Tests with 10-, 20-, and 30-micrograms Sch 21420 disks led to similar conclusions. The 30-micrograms Sch 21420 disks are recommended, with zone standards of less than or equal to 14 mm for the resistant category (minimal inhibitory concentration, greater than or equal to 32 micrograms/ml) and greater than or equal to 17 mm for the susceptible category (minimal inhibitory concentration, less than or equal to 16 micrograms/ml). If a minimal inhibitory concentration breakpoint of less than or equal to 8 micrograms/ml is preferred for defining the susceptible category, somewhat different zone standards may be used (less than or equal to 15 mm and greater than or equal to 19mm). Further evaluation documented the fact that tests with 30-micrograms amikacin disks predicted resistance or susceptibility to Sch 21420 almost as well as did a 30-micrograms Sch 21420 disk. Thus, the class concept of disk testing was judged to applicable, and routine testing with Sch 21420 may not be required.
Comparative in vitro activity of moxalactam, cefotaxime, cefoperazone, piperacillin, and aminoglycosides against gram-negative bacilli
Authors: Kurtz T O , Winston D J , Hindler J A , Young L S , Hewitt W L , Martin W J
Published: June 2012

The in vitro activities of four new beta-lactam antimicrobial agents (moxalactam, cefotaxime, cefoperazone, and piperacillin) and the aminoglycosides against 744 recent clinical isolates of facultative gram-negative bacilli were compared simultaneously by the agar dilution method. The major in vitro difference of these newer beta-lactam compounds appeared to be their antipseudomonal activity; cefoperazone was the most active, whereas cefotaxime had the least potency. The aminoglycosides, however, had the most effective in vitro activity on a weight basis against Pseudomonas aeruginosa.
Quantitative correlation between penicillin resistance and beta-lactamase activity specified by the R plasmids R1, R1 bla-45, and RP1 in Escherichia coli K-12
Authors: Crowlesmith I , Howe T G
Published: June 2012

A mutant of the R plasmid R1 which synthesizes a beta-lactamase with altered kinetic characteristics was isolated. The level of penicillin resistance specified by this plasmid was correctly predicted from the properties of the wild-type R1 according to a simple theoretical model published by Zimmermann and Rosselet (Antimicrob. Agents Chemother. 12:368--372, 1977). The model also accounts for the high level of penicillin resistance specified by the R plasmid RP1.
Gentamicin Uptake in Wild-Type and Aminoglycoside-Resistant Small-Colony Mutants of
Staphylococcus aureus
Authors: Miller Michael H. , Edberg Stephen C. , Mandel Laura J. , Behar Caren F. , Steigbigel Neal H.
Published: June 2012

Gentamicin uptake and killing were studied in aminoglycoside-susceptible wild-type
Staphylococcus aureus
strains and aminoglycoside-resistant small-colony mutants selected by gentamicin from these strains. In wild-type
S. aureus
three phases of gentamicin accumulation were noted, and killing occurred during the last and most rapid phase of uptake. Uptake and killing were abolished by anaerobic growth and sodium azide, suggesting that energy-dependent active drug transport required respiration. Treatment of wild-type strains with the uncouplers
N,N
′-dicyclohexyl carbodiimide (DCCD) and carbonyl cyanide-
m
-chlorophenyl hydrazone showed disparate effects on gentamicin uptake, producing enhanced and diminished accumulations, respectively. Small-colony mutants demonstrated markedly deficient uptake compared with the wild-type strains and were not killed by gentamicin in concentrations up to 10 μg/ml. Several classes of aminoglycoside-resistant mutant strains are described. One mutant strain was a menadione auxotroph which, when grown in the presence of menadione, exhibited normal gentamicin uptake and killing. Gentamicin uptake and killing in this strain were abolished by KCN when the strain was grown in a medium supplemented with menadione. The membrane adenosine triphosphatase inhibitor DCCD was lethal for this mutant but not for other mutants or wild-type strains. Preincubation with menadione prevented the lethal effect of DCCD, and this strain demonstrated normal gentamicin accumulation when exposed to both DCCD and menadione. A second mutant strain demonstrated both gentamicin uptake and killing in the presence but not the absence of DCCD. Studies with small-colony mutants of
S. aureus
indicated that the defect in aminoglycoside uptake is very likely related to an inability to generate or maintain energized membranes from respiration. These studies suggest that the membrane energization associated with active aminoglycoside accumulation requires electron transport for the generation of a protonmotive force.
Comparative antimicrobial activity of O-demethylfortimicin A, a derivative of fortimicin A
Authors: Girolami R L , Stamm J M
Published: June 2012

The in vitro antimicrobial activity of O-demethylfortimicin A (ODMF), a derivative of fortimicin A, was compared with those of fortimicin A and gentamicin against a spectrum of 256 organisms. All three antibiotics were active in low concentrations against all strains of Enterobacteriaceae, Acinetobacter sp., and Staphylococcus aureus, with ODMF most active against Proteus mirabilis, indole-positive Proteus, and Providencia and gentamicin most active against other species. Activity of each of the antibiotics against group D streptococci was poor. The overall activity of ODMF was superior to that of fortimicin A for all groups of organisms examined and was most pronounced, approximately three-fold, against strains of Pseudomonas aeruginosa. Both ODMF and fortimicin A were resistant to the action of several aminoglycoside-inactivating enzymes, with the exception of 3-N-acetyltransferase-I. ODMF and fortimicin A showed similar rapid bactericidal effects at multiples of the minimum inhibitory concentration and equivalent synergistic activity against enterococci when combined with penicillin G. The combination of carbenicillin with ODMF, fortimicin A, or gentamicin was synergistic for approximately 80% of the P. aeruginosa strains tested. Inactivation of ODMF and fortimicin A when combined with carbenicillin in vitro was minimal or absent, whereas gentamicin was substantially inactivated under similar conditions. ODMF, fortimicin A, and gentamicin exhibited protective activity in mice infected with Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, S. aureus, or P. aeruginosa. Gentamicin was the most active, followed by ODMF and fortimicin A. The superior in vitro activity of ODMF compared with fortimicin A against P. aeruginosa was confirmed in vivo.
Susceptibility of Eikenella corrodens to newer beta-lactam antibiotics
Authors: Goldstein E J , Gombert M E , Agyare E O
Published: June 2012

In vitro susceptibility testing of 28 strains of Eikenella corrodens by the agar dilution technique showed that all strains were uniformly susceptible to penicillin, ticarcillin, cefoxitin, cefotaxime, N-formimidoyl thienamycin, and moxalactam and resistant to clindamycin and cefadroxil. Cefoperazone, piperacillin, and mezlocillin showed good activity, with some strains relatively resistant. Bacampicillin and cefamandole showed relatively poor activity.
In vitro susceptibility of Haemophilus equigenitalis, the causative organism of contagious equine metritis 1977, to antimicrobial agents
Authors: Dabernat H J , Delmas C F , Tainturier D J , Lareng M B
Published: June 2012

The in vitro susceptibility of recent clinical isolates of Haemophilus equigenitalis to various antimicrobial agents was determined by the disk diffusion test and the World Health Organization-International Collaborative Study agar dilution procedure. Ampicillin and tetracycline were the most active drugs. All strains were susceptible to beta-lactam antibiotics, chloramphenicol, trimethoprim-sulfamethoxazole, nalidixic acid, nitrofurantoin (Furadantin), and bacitracin. All but two strains were resistant to streptomycin, whereas all strains were susceptible to the other aminocyclitol antibodies. All strains were resistant to clindamycin, lincomycin, and metronidazole.
Pharmacokinetics of moxalactam in subjects with various degrees of renal dysfunction
Authors: Bolton W K , Scheld W M , Spyker D A , Overby T L , Sande M A
Published: June 2012

We have examined the pharmacokinetics of moxalactam (LY127935) in 36 subjects with various degrees of renal dysfunction. Creatinine clearance (Ccr)/1.73 m2 ranged from zero to 135.8 ml/min. After a 1-g administration of moxalactam intravenously, the volume of distribution was 20.6 /+- 9.5 liters (0.28 liter/kg), and the mean half-life ranged from 3.1 h for subjects with Ccr greater than 65 ml/min to 19.3 h for subjects with Ccr less than 10 ml/min. The moxalactam clearance was closely correlated to Ccr (r = 0.93, P less than 0.0001) and excretion of antibiotic was 73.6 +/- 13% in normal subjects. Renal clearance accounted for 90% of moxalactam clearance in the normal subjects. A dosage schedule for administering moxalactam to patients with various degrees of renal dysfunction is provided.
Antimicrobial susceptibility of Campylobacter jejuni and Campylobacter fetus subsp. fetus to eight cephalosporins with special reference to species differentiation
Authors: Karmali M A , De Grandis S , Fleming P C
Published: June 2012

Agar dilution antimicrobial susceptibility testing showed that Campylobacter jejuni was significantly more resistant than Campylobacter fetus subsp. fetus (intestinalis) to cephalosporin C, cephaloridine, cephalothin, cefazolin, and cefamandole. No species differences in susceptibility were noted with cephalexin, cefotaxime, and cefoxitin. Rapid species differentiation on the basis of an antibiogram could be achieved with the disk diffusion method. C jejuni failed to produce a zone of inhibition around a 30-microgram cephalothin disk but produced a significant zone around a 30-microgram nalidixic acid disk. C. fetus subsp. fetus (intestinalis) produced exactly the reverse pattern.
Comparative nephrotoxicities of dibekacin, amikacin, and gentamicin in a rat model
Authors: Rankin L I , Luft F C , Yum M N , Isaacs L L
Published: June 2012

The nephrotoxicity of dibekacin was compared with those of gentamicin and amikacin in a rat model. The doses used were 3, 10, and 30 times the suggested human therapeutic dose on a weight basis. Indices of glomerular and tubular function failed to clearly differentiate the drugs. Dibekacin and gentamicin produced equally severe injury to the renal tissue. Slightly less damage occurred with amikacin.
Evaluation of cefoxitin nephrotoxicity in experimentally induced renal failure
Authors: Ormrod D J , Miller T E
Published: June 2012

The nephrotoxicity of cefoxitin was studied in a rat model of impaired renal function. Two levels of renal impairment were produced: "moderate," with blood urea concentrations of 100 to 150 mg/100 ml (16.7 to 25.1 mmol/liter) and glomerular filtration rates 25 to 35% of normal, and "severe," with blood urea concentrations greater than 150 mg/100 ml (greater than 25.1 mmol/liter) and glomerular filtration rates 10 to 20% of normal. Sham-operated animals were used as controls. Three dose schedules of cefoxitin were administered to these controls--500, 1,000, and 2,500 mg/kg per day administered as a divided dose for 5 days. Doses given to the moderately and severely uremic animals were adjusted so that serum levels of cefoxitin were similar to those attained in the sham-operated control animals. Concentrations of urea and creatinine in blood, glomerular filtration rates, and the urinary concentrating capacities of the experimental animals were monitored before and after cefoxitin treatment. There was no evidence of nephrotoxicity in even the most challenging experiment, in which blood serum levels of cefoxitin reached 2,000 microgram/ml in animals, with 15% renal function. These findings support available clinical data, suggesting that cefoxitin can be administered safely to patients with compromised renal function.
Ribosomal binding region for the antibiotic tiamulin: stoichiometry, subunit location, and affinity for various analogs
Authors: Högenauer G , Ruf C
Published: June 2012

Equilibrium dialysis experiments with a highly purified preparation of labeled tiamulin, a semisynthetic derivative of the antibiotic pleuromutilin, and Escherichia coli ribosomes allowed the determination of two binding sites for the drug. The binding reaction showed a cooperative effect. Of the two subunits, the 50S particle was able to bind the antibiotic in a 1:1 stoichiometry. Hence, the 50S subunit contributed predominantly to the binding energy which held the antibiotic to the ribosomes. The 30S subunit, showing no strong affinity for the drug, may be needed for the generation of the second binding site in the 70S particle. If depleted of ammonium ions, 70S ribosomes lost their binding capacity for the antibiotic. The attachment sites for tiamulin could be restored by heating the ribosomes to 40 degrees C in the presence of either ammonium ions or the antibiotic. Other pleuromutilin derivatives displaced labeled tiamulin from its ribosomal binding sites. By quantifying this competition, the relative affinity of various pleuromutilin derivatives for E. coli ribosomes was determined. The binding correlated with the minimal inhibitory concentrations of these compounds against E. coli. When compared with the minimal inhibitory concentrations of these compounds against E. coli. When compared with the minimal inhibitory concentrations against E. coli. When compared with the minimal inhibitory concentrations against Staphylococcus aureus, the correlation was less strict, but the same trend prevailed. These results suggest that the antibacterial activities of various pleuromutilin derivatives on a given test organism are mainly determined by the strength of binding to the ribosomes within the bacterial cell.
Susceptibility of shigellae to mecillinam, nalidixic acid, trimethoprim, and five other antimicrobial agents
Authors: Hansson H B , Walder M , Juhlin I
Published: June 2012

A total of 199 strains of shigella (1 Shigella dysenteriae, 15 S. boydii, 47 S. flexneri, and 136 S. sonnei) isolated in Malmö, Sweden, within a 3-year period (1977 through January 1980) were tested with the agar plate dilution method for susceptibility to commonly used and newer antimicrobial agents. Mecillinam, nalidixic acid, and trimethoprim had the best in vitro activity. S. flexneri dominated among strains resistant to three or more antimicrobial agents and were less susceptible to ampicillin, chloramphenicol, and doxycycline than other types studied. Sixty-four percent of the strains were resistant to sulfamethoxazole. In vitro, a synergistic effect with trimethoprim was shown only in strains susceptible to sulfamethoxazole. The amidinopenicillin mecillinam was highly active against shigellae. When resistance occurred, it was linked to ampicillin in 17 of 18 strains. The quinolines, here represented by nalidixic acid, might be the drugs of choice.
In vitro antibacterial activity of fluorinated analogs of chloramphenicol and thiamphenicol
Authors: Syriopoulou V P , Harding A L , Goldmann D A , Smith A L
Published: June 2012

We evaluated the in vitro antimicrobial activity of Sch 24893, Sch 25298, and Sch 25393, three novel analogs of chloramphenicol and thiamphenicol. All of the analogs had minimal inhibitory concentrations of less than or equal to 10 micrograms/ml for 18 chloramphenicol-thiamphenicol-resistant strains of Shigella dysenteriae and 21 strains of resistant Salmonella typhi. The analogs were also more active than were chloramphenicol and thiamphenicol against chloramphenicol-resistant enteric bacteria, including six strains of Escherichia coli, seven strains of Klebsiella pneumoniae, and two strains of Enterobacter cloacae. Fifty-three strains of ampicillin-resistant Haemophilus influenzae were uniformly susceptible to chloramphenicol, thiamphenicol, and the three analogs. Sch 25298 was the most active compound tested (minimal inhibitory concentration, 0.5 microgram/ml for all strains). Four of seven chloramphenicol-thiamphenicol-resistant Haemophilus strains were susceptible to the fluorinated analogs. Of the three Haemophilus strains which were resistant to chloramphenicol, thiamphenicol, and the analogs, two contained less than 10% of the chloramphenicol acetyltransferase activity of the strains which were resistant to only chloramphenicol and thiamphenicol. We conclude that fluorinated analogs of chloramphenicol and thiamphenicol have considerable in vitro activity against a broad spectrum of chloramphenicol-thiamphenicol-resistant, gram-negative bacteria.
Effects of rifampin on biliary lipids in humans
Authors: von Bergmann K , Fierer J , Mok H Y , Grundy S M
Published: June 2012

Because the action of rifampin induces hepatic microsomal enzymes, a study was carried out in four patients to determine whether this drug alters the composition of biliary lipids. Several different measurements were made while patients were both on and off rifampin therapy for various infective processes. These measurements included multiple determinations of lipid composition of gallbladder bile, the relative proportions f individual bile acids, and kinetics of cholic acid and chenodeoxycholic acid. In all four patients, the saturation of gallbladder bile increased during rifampin treatment, and the bile consistently became supersaturated. The relative portions of chenodeoxycholic acid and cholic acid were essentially unchanged by treatment, but total synthesis of bile acids increased in three tested patients with rifampin therapy. These results indicate that rifampin increases saturation of bile with cholesterol, but this increase is not due to a reduction in bile acid production.
Amikacin sulfate levels in human serum and bile
Authors: Bermúdez R H , Lugo A , Ramírez-Ronda C H , Amadeo J A , Morales J
Published: June 2012

Amikacin levels in blood and bile were measured in 10 patients who underwent cholecystectomy and T-tube drainage. Each patient received 500 mg of amikacin intravenously 12 h preoperatively, during surgery, and every 12 h thereafter for four more doses. Average levels of amikacin in bile were 8.3 micrograms/ml at 1 h after the intraoperative dose, with a bile/serum ratio of 0.44. Postoperative doses at 1 h produced levels in bile of 3.8 to 4.2 micrograms/ml, with a bile/serum ratio of 0.15 to 0.22. Levels in bile decreased at a rate lower than levels in blood, and bile/serum ratios increased from 0.54 at 2 h to 0.93 at 12 h. Amikacin accumulated in bile at 6 h after the intravenous dose.
Isolation of Antibiotic-Resistant
Salmonella krefeld
from Clinical Veterinary Materials
Authors: Mathewson John J. , Simpson Russell B. , Roush David A.
Published: June 2012

Six isolations of
Salmonella krefeld
were made from clinical veterinary specimens. These isolates were multiply resistant to several antimicrobial agents commonly used to treat salmonellosis.
Inconsistency of Synergy Between the
β
-Lactamase Inhibitor CP-45,899 and
β
-Lactam Antibiotics Against Multiply Drug-Resistant
Enterobacteriaceae
and
Pseudomonas
Species
Authors: Fass Robert J.
Published: June 2012

Synergy between CP-45,899 and ampicillin or newer
β
-lactam antibiotics against multiply drug-resistant
Enterobacteriaceae
and
Pseudomonas
species was inconsistent. In contrast, synergy between CP-45,899 and ampicillin against
β
-lactamase-producing strains of
Haemophilus influenzae
type b and
Bacteroides fragilis
was consistent and marked.
Prevention of acute and chronic ascending pyelonephritis in rats by aminoglycoside antibiotics accumulated and persistent in kidneys
Authors: Bille J , Glauser M P
Published: June 2012

Gentamicin, because it is stored in renal tissues, can prevent acute retrograde pyelonephritis. Since different aminoglycosides accumulate and persist to various degrees in the kidney parenchyma, the prophylactic activities of gentamicin, tobramycin, amikacin, and netilmicin were compared. The four antibiotics were given intramuscularly to rats 3 days before initiating ascending unilateral pyelonephritis with Escherichia coli. Despite different degrees of renal accumulation at the time of infection (tobramycin and amikacin accumulated significantly less), all four aminoglycosides displayed similar protection against ascending pyelonephritis. This protection was conferred in the absence of active antibiotic detectable in the urine and was therefore attributed to antibiotic stored in the renal parenchyma. Those animals that developed pyelonephritis despite aminoglycoside prophylaxis had less severe acute kidney infection and inflammation. This resulted 3 months later in an almost complete protection against renal scarring (chronic pyelonephritis). These results in rats suggest that renal accumulation and persistence of aminoglycosides may be used to advantage in the prophylaxis or in the treatment of kidney infections.