bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative activities of cefotiam and cefazolin against urinary tract infections with Proteus mirabilis in mice
Authors: Iwahi T , Tsuchiya K
Published: June 2012

The therapeutic effect of cefotiam on experimental urinary tract infections with Proteus mirabilis IFO 3849 in mice was compared with that of cefazolin. The minimal inhibitory concentrations of cefotiam and cefazolin against the test organism were 1.56 and 25 micrograms/ml, respectively. Beginning 3 days after infection, various doses of each cephalosporin were given subcutaneously twice a day for 5 days. Doses of 100 mg of cefotiam per kg or more sterilized the urine within 3 days and effected a marked reduction or complete eradication of bacteria in the bladder walls and kidneys of mice sacrificed the day after treatment was terminated. A dose of cefazolin greater than 800 mg/kg was required for equivalent therapeutic results. Clearance of bacteria from urinary tract organs was as rapid or more rapid with 50-mg/kg doses of cefotiam as with 200-mg/kg doses of cefazolin. Much more rapid clearance was attained with 200-mg/kg doses of cefotiam. The concentrations of cefotiam attained in plasma, kidney, and urine were lower than the cefazolin levels achieved at an equivalent dose. The superiority of cefotiam over cefazolin in treatment of experimental urinary tract infections appears to be due to its greater activity against the test organism.
Comparative nephrotoxicities of high-dose netilmicin and tobramycin in rats
Authors: Parker R A , Gilbert D N , Houghton D C , Porter G A , Bennett W M
Published: June 2012

The nephrotoxic potentials of netilmicin and tobramycin given in doses of 180 mg/kg per day for up to 14 days were compared in Fischer rats. At this dosage, tobramycin produced mortality and significant changes in renal structure and function; netilmicin evoked minimal nephrotoxicity.
Effect of clavulanic acid on minimal inhibitory concentrations of 16 antimicrobial agents tested against Legionella pneumophila
Authors: Pohlod D J , Saravolatz L D , Quinn E L , Somerville M M
Published: June 2012

A total of 15 Legionella pneumophilia isolated were tested against 16 antimicrobial agents used singly and in combination with clavulanic acid. When combined with clavulanic acid, 4 of the 16 antimicrobial agents produced no enhanced effect. However, the minimal inhibitory concentrations of 12 of the antimicrobial agents were reduced by one-half to one-third when in combination with clavulanic acid. These reductions reflected only a one-dilution decrease, however, in the original minimal inhibitory concentrations. Thus, clavulanic acid combinations appear to be only nominally effective beta-lactamase inhibitors against L. pneumophilia.
Incidence of thymidine-dependent enterococci detected on Mueller-Hinton agar with low thymidine content
Authors: Haltiner R C , Migneault P C , Robertson R G
Published: June 2012

It was observed that 10% of urine culture isolates of enterococci tested for antimicrobial susceptibility failed to grow on commercially prepared Mueller-Hinton agar with low levels of thymidine and thymine. All strains could utilize exogenous thymidine and thymine and required only low levels (0.4-microgram disk) to support growth. All thymidine-thymine-requiring strains were resistant to trimethoprim-sulfamethoxazole.
Pharmacokinetics of cefmetazole in normal subjects and in patients with impaired renal function
Authors: Ohkawa M , Orito M , Sugata T , Shimamura M , Sawaki M , Nakashita E , Kuroda K , Sasahara K
Published: June 2012

The pharmacokinetics of cefmetazole, a new cephamycin antibiotic, were examined after a 1-h intravenous drip infusion of 1 g to 5 healthy volunteers with normal renal function and 16 patients with impaired renal function. Peak serum concentrations were obtained at the end of the infusion in all subjects, regardless of their renal function. Approximately 70% of the infused dose was excreted in the urine within 6 h in healthy volunteers. The pharmacokinetic parameters of cefmetazole were derived by analyzing elimination data, with a one-compartment open model. The mean serum half-life of cefmetazole in healthy volunteers was 0.81 h. A significant correlation between the elimination rate constant and the creatinine clearance was demonstrated.
Modified polyriboinosinic-polyribocytidylic acid complex: modulation of toxicity for rabbits by alterations in components
Authors: Gatmaitan B G , Levy H B , Lerner A M
Published: June 2012

In an earlier study the physiological effects encountered in humans of a modified complex of polyriboinosinic acid-polyribocytidylic acid [poly(I)-poly(C)] with carboxymethylcellulose and poly-L-lysine [poly(ICLC) (9S)], namely, the induction of high titers of serum interferon along with fever and hypotension, were reproduced in rabbits. In the present studies, also in rabbits, we evaluated effects of complexes with homopolymer polyribonucleotide sedimentation coefficients decreasing from 9S to 6S and 4S. Modified complexes of carboxymethylcellulose and poly-L-lysine with decreasing molecular weights were also tested. In several studies diphenhydramine and indomethacin were administered concomitantly. These experiments showed that at a daily intravenous dose of 0.2 mg/kg the various preparations of poly(I)-poly(C) (9S) and poly(I)-poly(C) (6S) induced falls in blood pressure, but stabilized complexes of poly(I)-poly(C) (4S) did not. Alterations in the molecular weights of carboxymethylcellulose and poly-L-lysine n the modified complex and the concomitant administration of diphenhydramine did not influence the occurrence or severity of untoward reactions. In rabbits, poly(ICLC) (4S) along with indomethacin induced high titers of serum interferon without fever or hypotension.
Enhancement of activity against influenza viruses by combinations of antiviral agents
Authors: Hayden F G , Douglas R G , Simons R
Published: June 2012

In an investigation of alternative therapeutic approaches for the treatment of influenza virus infections, the antiviral activities of rimantadine hydrochloride, amantadine hydrochloride, ribavirin, and combinations of these drugs were assessed in vitro. Madin-Darby canine kidney cell monolayers were inoculated with recent isolates of influenza viruses at low multiplicities of infection, and virus titers were determined after 24 h. The combination of rimantadine and ribavirin resulted in an enhanced antiviral effect (a decrease in virus titer of > 1.0 log10 plaque-forming unit per ml at 24 h relative to the maximal effect of a single drug) against A/USSR/90/77/H1N1, A/Texas/1/77/H3N2, A/New Jersey/76/HSW1N1, and A/PR/834/H0N1 viruses. The degree of inhibition depended on the virus strain used, the drug concentrations, and the virus inoculum. Amantadine and ribavirin showed enhanced activity. Ribavirin in combination with high (50 micrograms/ml), but not low (1.56 to 25 micrograms/ml), concentrations of rimantadine showed an enhanced antiviral effect against B/Hong Kong/72 virus. An assay of Madin-Darby canine kidney cell proliferation in the presence of drugs showed that the enhanced inhibitory effect of drug combinations was not due to increased cytotoxicity.
Relationship between metronidazole metabolism and bactericidal activity
Authors: Chrystal E J , Koch R L , McLafferty M A , Goldman P
Published: June 2012

It has been suggested that the microbicidal effect of metronidazole is mediated by an intermediate in nitro group reduction. We have found that the addition of Escherichia coli enhances the lethal effect of metronidazole on Bacillus fragilis and suggest that this intermediate may form in one bacteria and kill another. Because acetamide forms during the reduction of metronidazole, we examined the possibility that the same partially reduced intermediate in metronidazole reduction may be both an intermediate in the formation of acetamide and the ultimate reactive form of metronidazole which is responsible for its bactericidal action. Thus, we determined the relationship between bacterial survival and the formation of acetamide when cultures of B. fragilis, Clostridium perfringens, and E. coli were incubated anaerobically in the presence of metronidazole. We found that the log of the early bacterial survival was proportional to the formation of acetamide. The rate of loss of metronidazole was not dependent on the concentration of bacteria in the medium, suggesting that any proposed intermediate formed at a rate which was proportional only to the concentration of metronidazole.
In vitro activity of N-formimidoyl thienamycin (MK0787)
Authors: Tally F P , Jacobus N V , Gorbach S L
Published: June 2012

The in vitro activity of N-formimidoyl thienamycin (MK0787), a stable congener of thienamycin, was determined against 200 species of aerobic and 84 species of anaerobic bacteria. The compound was highly active against resistant gram-negative bacilli, penicillin-resistant Staphylococcus aureus, enterococci, and anaerobic bacteria. The new derivative of thienamycin was more active than the parent compound, probably reflecting the stability of the analog.
Tentative interpretive standards for disk susceptibility tests with moxalactam (LY127935)
Authors: Barry A L , Thornsberry C , Jones R N , Gerlach E H
Published: June 2012

Moxalactam (LY127935; 6059-S) is a new beta-lactam antibiotic. We propose tentative zone standards for agar diffusion susceptibility tests with 30-microgram disks. The final selection of minimal inhibitory concentration breakpoints for definition of resistant and susceptible categories must await clinical experience with this drug. Some of the clinical questions to be answered are defined. A moderately susceptible (intermediate) category is proposed for those strains with minimal inhibitory concentrations of 16 or 32 microgram/ml (zones 15 to 22 mm in diameter). Strains with minimal inhibitory concentrations of greater than or equal to 64 microgram/ml are considered resistant, and those with minimal inhibitory concentrations of less than or equal to 8 microgram/ml are considered susceptible. Tests with 30-microgram disks did not satisfactorily separate strains with minimal inhibitory concentrations of 8 microgram/ml from strains requiring < 2 microgram/ml for inhibition, because the regression line became parabolic at concentrations of 2 microgram/ml and below. However, the disk tests were satisfactory for categorizing isolates into the above-described susceptible, moderately susceptible (intermediate), and resistant categories.
Effect of storage and changes in bacterial growth phase and antibiotic concentrations on antimicrobial tolerance in Staphylococcus aureus
Authors: Mayhall C G , Apollo E
Published: June 2012

Forty clinical isolates of Staphylococcus aureus were tested for tolerance to oxacillin and cephalothin by broth dilution susceptibility tests and killing curves. Most experiments were carried out with stationary-phase inocula, but nine tolerant isolates were retested with log-phase inocula. All 40 isolates were retested in killing curves at double the antibiotic concentrations used in initial tests. Isolates were retested for tolerance to oxacillin after storage at --70 degrees C for 1 year. In broth dilution tests, 23 of 40 (57.5%) and 20 of 40 (50%) isolates were tolerant to oxacillin and cephalothin, respectively. By killing curves, 25 of 40 (62.5%) and 22 of 40 (55%) isolates were tolerant to oxacillin and cephalothin, respectively. When nine tolerant isolates were retested with log-phase inocula, none manifested tolerance. Only 25 to 30% of the isolates were tolerant in killing curves performed with oxacillin and cephalothin at concentrations double those used in initial tests. After storage at --70 degrees C for 1 year, only two-thirds of the isolates remained tolerant. In isolates that remained tolerant, the degree of tolerance diminished to about 25% of that observed in initial tests.
Killing of oxacillin-exposed staphylococci in human polymorphonuclear leukocytes
Authors: Lorian V , Atkinson B
Published: June 2012

Twelve strains of Staphylococcus aureus isolated from patients and two collection strains were grown on membranes placed on agar containing subminimal inhibitory concentrations of oxacillin. Clusters of staphylococci held together by thick cross walls resulted. These organisms, as well as the same strains grown in the same way on drug-free medium (control), were eluted from the membranes and were incubated with human polymorphonuclear leukocytes (PMNs) from various donors. Phagocytosis was comparable for both staphylococci exposed to oxacillin and control staphylococci, but the killing effect was different. The staphylococci grown on membranes in the presence of oxacillin were less susceptible to killing than the control staphylococci, but the killing effect was different. The staphylococci grown on membranes in the presence of oxacillin were less susceptible to killing than the control staphylococci. After 0.5 and 1 h of incubation with PMNs, the killing rates for oxacillin-grown versus control staphylococci were 52 and 70% and 65 and 85%, respectively (P < 0.01). After 2 and 3 h of incubation, the killing was similar. Most clusters of staphylococci contain a few individual cells that are located in the center of the cluster and are surrounded by other staphylococci; therefore, they are protected from adverse agents in the environment. This could explain why the phagocytized clusters are less susceptible than control staphylococci to the killing effect of PMNs during the first hour of incubation. Oxacillin does not penetrate into PMNs and in the absence of the drug the cross walls lyse, liberating the constituent staphylococci. This coincides with the increase in the percentage of cluster killing by PMNs after 2 and 3 h of incubation.
Differences among Providencia species in their in vitro susceptibilities to five antibiotics
Authors: Penner J L , Preston M A
Published: June 2012

Significant differences among the three Providencia species (P. alcalifaciens, P. stuartii, and P. rettgeri) in antimicrobial susceptibilities to five antibiotics were shown. P. stuartii was the most resistant of the three species, and P. alcalifaciens was the most susceptible. P. rettgeri was similar to P. stuartii in susceptibilities to cefoxitin, cephalothin, and cefamandole but differed in showing greater susceptibilities to tobramycin and gentamicin. Cefoxitin (16 micrograms/ml) and cefamandole (16 micrograms/ml) inhibited a greater proportion of P. stuartii isolates than did cephalothin, tobramycin, or gentamicin. The susceptibilities of urea-positive isolates of P. stuartii resembled more closely the susceptibilities of urea-negative isolates of this species than those of P. rettgeri isolates, a finding consistent with the recent recommendation for transferring such urea-positive strains to P. stuartii. Among P. stuartii isolates, marked resistance to cefoxitin accompanied by susceptibility to cefamandole was predominantly restricted to isolates of one serotype (O55). The use of isolates that had been serotyped and classified according to recent proposals for taxonomic changes in the Proteeae provided for clearer demonstration of species differences in susceptibility.
Corynebacterium equi: in vitro susceptibility to twenty-six antimicrobial agents
Authors: Woolcock J B , Mutimer M D
Published: June 2012

The minimal concentrations of 26 antimicrobial agents required to inhibit growth of 100 isolates of Corynebacterium equi in vitro have been determined. The most active agents were penicillin G, doxycycline, erythromycin, lincomycin, and the aminoglycosides.
Cefoperazone concentrations in bile and gall bladder wall after intravenous administration
Authors: Nakamura T , Hashimoto I , Sawada Y , Mikami J , Bekki E , Hirasawa S , Abe H , Watanabe Y
Published: June 2012

Cefoperazone concentrations in the common duct bile, gall bladder bile, and gall bladder wall were determined in four patients with cholelithiasis and one patient with carcinoma of the head of the pancreas, all of whom had normal renal functions. Within 65 min after a 1-g intravenous administration, maximum concentrations ranged from 373.4 to 3,100 micrograms/ml in common duct bile and from 6.8 to 680 micrograms/ml in gall bladder bile. Cefoperazone concentrations per gram of the gall bladder wall ranged from 16.8 to 48.0 micrograms.
Evaluation of rosaramicin phosphate in treatment of experimental syphilis in rabbits
Authors: Baughn R E , Musher D M , Adams C B , Knox J M
Published: June 2012

The in vivo activity of rosaramicin phosphate in disseminated and localized Treponema pallidum infections in rabbits was compared with that of penicillin G benzathine. Rabbits were injected either intradermally or intravenously to establish infection. Groups of four animals each then received either two weekly injections of 200,000 U of penicillin G benzathine, injections of 12.5 or 25 mg of rosaramicin per kg of body weight twice a day for 10 days, or no antibiotic therapy. Treatment of the intradermal and intravenous infections was initiated on days 7 and 14 postinfection, respectively. With both infection models, striking differences were noted between the untreated control rabbits and the three groups receiving treatment; no discernible differences, however, were detected among any of the treated groups. Rabbits that had been infected intravenously did not develop disseminated lesions or orchitis after treatment, and chancres produced by intradermal infection regressed and healed rapidly after the initiation of therapy. Continued increases in treponemal and nontreponemal antibody titers posttreatment did not occur in any of the treated rabbits. Infectivity studies also suggested that the lymph nodes and testes of treated animals were free from infectious organisms. Overall, at the dosage regimens employed, both rosaramicin and penicillin G benzathine appeared to effect complete control of the experimental disease.
Neisseria gonorrhoeae strains isolated in Hong Kong: in vitro susceptibility to 13 antibiotics
Authors: Ng W S , Anton P , Arnold K
Published: June 2012

Fifty-five Neisseria gonorrhoeae strains isolated in Hong Kong over a period of 6 months were tested for their in vitro susceptibility to 13 antimicrobial agents by the agar dilution method. Six strains were beta-lactamase producing. In addition, five beta-lactamase strains from Singapore were tested. Among the non-beta-lactamase-producing strains, 34 (62%) had intermediate resistance to penicillin, with minimal inhibitory concentrations (MICs) ranging from 0.125 to 0.5 microgram/ml, and 15 strains were fully susceptible to penicillin (MICs, 0.015 to 0.06 microgram/ml). The MICs of penicillin for all beta-lactamase-producing strains were 2 microgram/ml, and the strains were resistant to ampicillin. Although a direct correlation between the MICs for resistance to penicillin and the other antibiotics tested was not observed, the gonococci isolated in Hong Kong were notably more resistant to tetracycline and streptomycin than has been reported elsewhere, with 78% of strains requiring for inhibition an MIC of tetracycline of greater than 2 microgram/ml and 51% of the isolates requiring an MIC of streptomycin of greater than 128 microgram/ml. All strains were susceptible to spectinomycin and kanamycin as well as to sulfamethoxazole-trimethoprim (ratio, 19:1). Among the cephalosporins, the order of effectiveness was cefuroxime, cefamandole, and cefoxitin. The older generation of cephalosporins, cephradine and cephalexin, was the least effective: 45 and 37% of the strains, respectively, required for inhibition MICs of greater than or equal to 8 microgram/ml. Cefotaxime, a new parenteral cephalosporin, was the most active; the median MIC was at least 10-fold lower than that of cefuroxime.
Comparison of antibacterial and antiimmune effects of certain rifamycins
Authors: Kasik J E , Monick M
Published: June 2012

Comparison of the in vivo and in vitro immunosuppressive activities of the five rifamycins with their in vitro antibacterial and anti-ribonucleic acid polymerase activities indicated that correlation was poor. Examination of their activities on mitogen-induced blastogenesis in human peripheral blood leukocytes and inhibition of delayed-type hypersensitivity to partially purified protein derivative in immunized mice demonstrated that correlation was usually good. Antibacterial activity in cultures and the activities of the rifamycins inhibiting deoxyribonucleic acid-dependent ribonucleic acid polymerase appeared to correlate well. However, when these two types of activity, antiimmune and antibacterial, were compared, correlation was poor on occasion and indicated that the antiimmune activities and antibacterial activities of the rifamycins are probably not related.
Sensitive radioimmunoassay for vancomycin
Authors: Fong K L , Ho D H , Bogerd L , Pan T , Brown N S , Gentry L , Bodey G P
Published: June 2012

A radioimmunoassay for vancomycin has been developed which uses rabbit antiserum induced by vancomycin-bovine serum albumin conjugates and vancomycin labeled with 3H or 125I. Using either isotope, the method is simple and reproducible and has a sensitivity of 4 or 0.04 ng/ml, depending on the tracer used. This is 200- to 20,000-fold improvement in sensitivity compared with the most sensitive bioassay. Drug levels in serum or urine samples from patients receiving vancomycin can be determined by this assay procedure without processing. The data obtained with 3H and 125I labels were in good agreement. Patients' plasma vancomycin concentrations determined by radioimmunoassay correlated well with those determined by bioassay when the drug was administered intravenously. However, after oral administration the drug could be detected only by radioimmunoassay. The antiserum was evaluated for cross-reactivity with a wide variety of antibiotics and cancer chemotherapeutic agents, and no significant interference was found.
Antimicrobial susceptibility of Capnocytophaga
Authors: Forlenza S W , Newman M G , Horikoshi A L , Blachman U
Published: June 2012

Capnocytophaga (Bacteroides ochraceus, Center for Disease Control biogroup DF-1) is associated with sepsis in granulocytopenic patients and is isolated in large numbers from the affected periodontal pockets in patients with juvenile periodontosis. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of 17 antimicrobial agents for 13 strains of Capnocytophaga organisms were determined. In addition, the ratio of the MBC to the MIC for each antimicrobial agent was determined for each strain. At concentrations of 1 microgram/ml or less, penicillin, ampicillin, carbenicillin, erythromycin, and clindamycin killed 90% of the strains. At concentrations of 3.12 microgram/ml or less, tetracycline, metronidazole, cefoxitin, and chloramphenicol killed 90% of the strains. None of the aminoglycosides tested demonstrated antibacterial activity at 50 microgram/ml. Penicillin, ampicillin, carbenicillin, and cefoxitin exhibited MBC/MIC ratios of 4 or less with all strains. Erythromycin, tetracycline, and metronidazole exhibited MBC/MIC ratios of 4 or less for 12 of 13 strains. The MICs of cephalothin and cefazolin for 90% of the strains were 25 and 50 microgram/ml, respectively. The MBC/MIC ratios for these drugs were 4 or less for 12 of 13 and 7 of 13 strains, respectively. The MIC of cefamandole for 90% of the strains was 3.12 microgram/ml; however, only nine strains had an MBC/MIC ratio of 4 or less.
Grahamimycins: antibiotics from Cytospora sp. Ehrenb. W.F.P.L. 13A
Authors: Gurusiddaiah S , Ronald R C
Published: June 2012

Aerobic fermentation of cultures of Cytospora sp. Ehrenb. W.F.P.L. 13A produces a group of novel, broad-spectrum, dilactone, macrocyclic antibiotics. These compounds, named grahamimycins, were isolated from the culture medium by extraction with organic solvents and separated by chromatography. Three active components have been obtained in crystalline form and have been designated grahamimycins A, A1, and B. The most active of these, grahamimycin A, exhibited activity against 36 species of bacteria, 8 species of blue-green algae (cyanobacteria), and 2 species of green algae, and antifungal activity against 5 fungi. Studies on the growth of the Cytospora with respect to formation of antibiotic activity, and the isolation, characterization, and structure elucidation of the grahamimycins are described. These studies indicate that the grahamimycins are distinct from other known antibiotics and represent a new class of antibiotic structures.
Purification and Some Properties of a Cephalosporinase from
Proteus vulgaris
Authors: Matsubara Nobuyuki , Yotsuji Akira , Kumano Katsuhiko , Inoue Matsuhisa , Mitsuhashi Susumu
Published: June 2012

The purified cephalosporinase from
Proteus vulgaris
hydrolyzed a variety of cephalosporins, including cefuroxime, at a high level; its activity was inhibited by clavulanic acid.
Comparative Activities of AM-715 and Pipemidic and Nalidixic Acids Against Experimentally Induced Systemic and Urinary Tract Infections
Authors: Hirai Keiji , Ito Akira , Abe Yashuo , Suzue Seigo , Irikura Tsutomu , Inoue Matsuhisa , Mitsuhashi Susumu
Published: June 2012

Dose for dose, AM-715 was at least five times as active as pipemidic acid and nalidixic acid against systemic and urinary bladder-kidney infections in mice.
Combined in vitro effect of amphotericin B and rifampin on Cryptococcus neoformans
Authors: Fujita N K , Edwards J E
Published: June 2012

The combination of amphotericin B and rifampin was synergistic in vitro in both inhibiting and killing seven strains of Cryptococcus neoformans by the checkerboard microtitration technique.
Increase in colony-forming units of Candida albicans after treatment with polyene antibiotics
Authors: Brajtburg J , Elberg S , Medoff G , Kobayashi G S
Published: June 2012

Polyene antibiotics, at concentrations which do not cause detectable toxic effect, induce an increase in the number of colon-forming units of yeast cells of Candida albicans. This effect, which we attribute to an increase in plating efficiency, is probably caused by binding of the polyenes to fatty acids in the cell wall of fungi.
Suction skin blister, skin window, and skin chamber techniques to determine extravascular passage of cefotaxime in humans
Authors: Frongillo R F , Galuppo L , Moretti A
Published: June 2012

We report the results obtained in comparative study on the extravascular passage of cefotaxime, employing three different methods: suction skin blister, skin window, and skin chamber. Applying the skin blister method in two different ways, we also studied the influence that suction pressure and time lapse between blister formation and antibiotic injection had on the results obtained in order to standardize the method and establish repeatability of the results. Using the skin chamber method, we studied the influence that the different protein contents in the fluid used to fill the skin chamber had on extravascular concentrations.
Cefmenoxime (SCE-1365), a novel broad-spectrum cephalosporin: in vitro and in vivo antibacterial activities
Authors: Tsuchiya K , Kondo M , Kida M , Nakao M , Iwahi T , Nishi T , Noji Y , Takeuchi M , Nozaki Y
Published: June 2012

The activity of cefmenoxime (SCE-1365), 7 beta-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid, was compared with that of other cephalosporins. Cefmenoxime exhibited high activity against a wide variety of gram-positive and gram-negative bacteria. The in vitro activity of cefmenoxime against Streptococcus pyogenes, Haemophilus influenzae, and Enterobacteriaceae, including indole-positive Proteus, Serratia marcescens, Enterobacter cloacae, and Citrobacter freundii, was 10 to 1,000 times greater than that of several other cephalosporins. Against Pseudomonas aeruginosa, cefmenoxime showed activity two to four times that of sulbenicillin and carbenicillin but less than that of cefsulodin. Variation in pH, addition of horse serum, and type of growth medium had definite effects on the activity of cefmenoxime, and the inoculum size affected the activity against bacterial species. In Escherichia coli cefmenoxime showed marked affinity for penicillin-binding protein 3 (PBP-3), followed by PBP-1 (1A and 1B). This affinity profile was well correlated with its filamentous cell-forming activity under extremely low drug concentrations and with its bactericidal activity against microorganisms. The high in vitro activity of cefmenoxime was reflected in the degree of protection observed in mice infected intraperitoneally with a wide variety of gram-positive and gram-negative bacteria. Furthermore, cefmenoxime showed good therapeutic activity against infection models in mice such as respiratory tract infection caused by Klebsiella pneumoniae and urinary tract infection caused by Proteus mirabilis.
Genetic study of plasmid-associated zonal resistance to lincomycin in Streptococcus pyogenes
Authors: Malke H , Reichardt W , Hartmann M , Walter F
Published: June 2012

The phenomenon of zonal resistance to lincomycin, which is characteristic of most clinical isolates with lincomycin resistance in Streptococcus pyogenes, has been studied. These strains grow within a defined concentration range of lincomycin (approximately 60 to 200 microgram/ml), or at lincomycin concentrations below the minimal inhibitory concentration for susceptible strains. It is shown that the zonal growth phenomenon is a stable phenotype and results from induction of resistance only within the zonal concentration range of lincomycin. These strains also possess inducible resistance to erythromycin which is nonzonal in character. One-step mutations to constitutive resistance have been isolated which are of two types: constitutive for lincomycin or for erythromycin, but not for both. Those strains with constitutive erythromycin resistance retain their zonal resistance for lincomycin. Mutants doubly constitutive for both lincomycin and erythromycin can be obtained by a second mutational step from either of the singly constitutive mutants. Satellite deoxyribonucleic acid has been shown to be present in the zonal resistant strains. A plasmid, pSM10419, of 14.9 megadaltons, has been isolated from one of the doubly constitutive mutants and used to jointly transform Streptococcus sanguis strain Challis to constitutive resistance to both lincomycin and erythromycin. From this, a multicopy plasmid of reduced size, pSM10 (5.4 megadaltons), which retains its resistance phenotype, has been isolated and mapped with restriction endonucleases HindIII (three sites), EcoRI (one site), KpnI (one site), and HpaI (one site). The staphylococcal plasmid pC221 (2.9 megadaltons; chloramphenicol resistant) has been fused to pSM10 at the EcoRI site resulting in a chimeric plasmid, pSM10221 (8.3 megadaltons), which retains resistance to chloramphenicol, erythromycin, and lincomycin. pSM10 is therefore suggestive as an effective cloning vehicle for the genus Streptococcus.
Metabolic regulation in tylosin-producing Streptomyces fradiae: phosphate control of tylosin biosynthesis
Authors: Vu-Trong K , Bhuwapathanapun S , Gray P P
Published: June 2012

The effects of increased concentration of inorganic phosphate on the biosynthesis of tylosin, the level of the intracellular adenylates, the energy charge, and the activities of enzymes involved in the synthesis of tylonolide precursors were studied in Streptomyces fradiae NRRL 2702. No metabolic response was observed when elevated levels of inorganic phosphate were added in idiophase. Increased initial levels of inorganic phosphate suppressed tylosin production and markedly increased the levels of the adenylates, although the adenylate energy charge was unchanged. Higher growth and glucose uptake rates were also observed. The activities of methylmalonyl-coenzyme A carboxyltransferase (EC 2.1.3.1) and propionyl-coenzyme A carboxylase (EC 6.4.1.3) were suppressed by the increased concentration of inorganic phosphate. The results indicated that the rate of tylosin synthesis was inversely related to the absolute level of the adenylates rather than to the energy charge.
Cefoxitin disposition during peritoneal dialysis
Authors: Greaves W L , Kreeft J H , Ogilvie R I , Richards G K
Published: June 2012

The pharmacokinetic disposition of 2 g of cefoxitin administered intravenously over 30 min was determined in six patients undergoing continuous ambulatory peritoneal dialysis for chronic renal failure. During the 6-h dialysate dwell time after the drug infusion, the mean apparent volume of distribution for cefoxitin was 0.267 liter/kg (range, 0.201 to 0.325 liter/kg), and the mean elimination t1/2 from plasma was 7.8 h (range, 5.5 to 13.1 h). The peritoneal clearance, averaging 1.51 ml/min (range, 0.58 to 2.35 ml/min), was only 7.4% of the mean plasmas clearance of cefoxitin. Cefoxitin clearance was reduced in patients with renal failure and was not increased by peritoneal dialysis.
Pharmacokinetics of piperacillin in patients with moderate renal failure and in patients undergoing hemodialysis
Authors: Giron J A , Meyers B R , Hirschman S Z , Srulevitch E
Published: June 2012

The pharmacokinetics of piperacillin administered intravenously were studied in five patients with stable mild to moderate renal impairment and in five patients undergoing hemodialysis. Patients with stable renal failure given 1 g of piperacillin intravenously had peak serum concentrations within 30 min ranging from 78 to 280 micrograms/ml. The mean serum half-life was 3.57 +/- 1.36 h; the mean apparent volume of distribution was 28.6 +/- 13.5 liters/100 kg; and the plasma clearance was 4.10 +/- 1.46 liters/h per 1.73 m2. Neither serum half-life nor clearance correlated with serum creatinine, implying significant nonrenal elimination. Patients undergoing hemodialysis had peak serum concentrations within 30 min of 66 to 138 micrograms/ml after 1 g of piperacillin infused intravenously. During hemodialysis, the serum half-life was 3.6 +/- 2.5 h; the mean apparent volume of distribution was 26.7 +/- 16.7 liters/100 kg; and the plasma clearance was 3.28 +/- 0.76 layers/h per 1.73 m2. Mean hemodialysis clearance was 0.484 +/- 0.282 liters/h per 1.73 m2, and only 10.0 +/- 5.3% of the total dose could be recovered in the dialysate.
Analysis of the in vitro interaction between vancomycin and cholestyramine
Authors: King C Y , Barriere S L
Published: June 2012

Vancomycin and cholestyramine have been utilized both alone and in combination for the treatment of antibiotic-associated pseudomembranous colitis. Previous work for the treatment of antibiotic-associated pseudomembranous colitis. Previous work has demonstrated significant binding of vancomycin by the anion-exchange resin. The antibacterial activity of vancomycin was markedly reduced when the suspension was centrifuged and the supernatant was tested for antibacterial activity. This study confirmed these findings but demonstrated that there was no immediate loss of antibacterial activity of bound vancomycin. The degree of inactivation appeared to be dependent upon the duration of incubation of vancomycin and cholestyramine in the testing system.
Treatment of experimental Salmonella typhimurium infection with mecillinam and ampicillin
Authors: Butler T , Shuster C W , Dixon P
Published: June 2012

The activities of mecillinam and ampicillin, alone and in combination, were evaluated in mice infected with the LT-2 strain of Salmonella typhimurium. The minimal inhibitory concentrations of mecillinam and ampicillin for this strain were, respectively, 6.2 and 0.4 microgram/ml of culture medium. In vitro synergy was demonstrated. CF-1 mice inoculated intraperitoneally with 10(4) colony-forming units of the LT-2 strain were used in the therapeutic assessments. Treatment of subgroups with graded doses of the respective penicillins or their combination was initiated 24 h after inoculation and repeated at 6-h intervals for 5 consecutive days. Animals were observed during 21 days for mortality or sacrificed for quantitative cultures of spleen homogenates at the end of the treatment. Ampicillin in doses of greater than or equal to 0.03 mg and mecillinam in doses of greater than or equal to mg reduced mortality rates from 77% in the saline-treated controls to a range of 0 to 4% (P less than 0.05). The same doses of antibiotics also extended the median times to death and lowered significantly the means of splenic bacterial counts. When both drugs were combined in doses that were partially effective or subinhibitory alone, no synergistic effects were observed. These results showed that mecillinam and ampicillin given alone were effective in treating S. typhimurium infection but that combinations of the two drugs were not synergistic in controlling the course of infections.
Effects of Ethambutol on Phospholipid Metabolism in
Mycobacterium smegmatis
Authors: Kilburn James O. , Takayama Kuni , Armstrong Emma Lee , Greenberg Joseph
Published: June 2012

Soon after
Mycobacterium smegmatis
was exposed to ethambutol, the synthesis of cardiolipin and phosphatidylinositol dimannoside declined. The synthesis of phosphatidylethanolamine continued, but the drug caused this phospholipid to leak out of the cells.
Differences between ceftizoxime and its stereoisomer in antibacterial activity and affinity for penicillin-binding proteins
Authors: Shigi Y , Kojo H , Wakasugi M , Nishida M
Published: June 2012

A new cephalosporin derivative, ceftizoxime (syn FK 749), and its anti isomer, FR 14060, were compared in antibacterial activity, outer membrane permeability, stability to beta-lactamases, and affinity for penicillin-binding proteins (PBPs), using Escherichia coli NIHJ JC-2 and Enterobacter cloacae 58-5 as the test organisms. Although ceftizoxime was superior in antibacterial activity to FR 14060, no marked differences between the two agents were found in outer membrane permeability and stability to cephalosporinase. However, the affinity for PBPs and stability to penicillinase of ceftizoxime and FR 14060 differed significantly. Concentrations of ceftizoxime required to reduce [14C]penicillin G binding by 50% were below 1 microgram/ml for PBPs 1a and 1bs of E. cloacae 58-5 and below 3.2 microgram/ml for PBPs 1a and 1bs of E. coli NIHJ JC-2. A more than 10-fold-higher concentration of FR 14060 was required for 50% reduction of (14C]penicillin G binding to PBP 1bs of strains tested. Ceftizoxime was severalfold more stable than FR 14060 to penicillinase, but the antibacterial activity of both drugs against penicillinase-producing E. coli was as strong as against non-penicillinase-producing E. coli. These results indicate that the difference between the two compounds in antibacterial activity is likely to be due to differences in their abilities to inhibit peptidoglycan polymerization.
Comparison of in vitro activities of eight beta-lactamase-stable cephalosporins against beta-lactamase-producing gram-negative bacilli
Authors: Verbist L
Published: June 2012

In vitro activities of eight beta-lactamase-stable cephalosporins, cefoxitin, cefuroxime, cefotaxime, moxalactam, SCE-1365, cefoperazone, ceftazidime, and cefsulodin, were compared against selected cephalothin-resistant or beta-lactamase-producing gram-negative bacilli or both. SCE-1365, cefotaxime, moxalactam, and ceftazidime had very similar activities against Enterobacteriaceae; SCE-1365 displayed the highest activity, and ceftazidime displayed the lowest activity. These four antibiotics were about 20 times more active than cefoperazone and 50 to 100 times more active than cefoxitin and cefuroxime. Against Pseudomonas aeruginosa and the other Pseudomonas species, ceftazidime showed the highest activity by far, followed by cefsulodin and cefoperazone. A close parallel resistance against P. aeruginosa isolates was observed between piperacillin on the one hand and cefoperazone and cefsulodin on the other.
Pharmacokinetics of moxalactam in patients with renal insufficiency
Authors: Lam M , Manion C V , Czerwinski A W
Published: June 2012

Moxalactam pharmacokinetics were determined in 18 patients with renal insufficiency (creatinine clearance, 0 to 99 ml/min). Each patient was given 0.5 g of moxalactam intramuscularly. Drug half-life ranged from 4.1 to 49.1 h and correlated inversely with creatinine clearance (r = -0.97). Total body drug clearance ranged from 0 to 88 ml/min, and renal clearance ranged from 0 to 57 ml/min. In four patients studied during hemodialysis, drug half-life was 21.7 +/- 7.5 h (mean +/- standard error) between dialyses and 4.4 +/- 0.5 h during dialysis. Moxalactam dialysance averaged 44 +/- 2 ml/min per m2 of dialyzer surface area, and approximately 50% of the drug was removed during a single hemodialysis. We confirmed that moxalactam is eliminated from the body primarily by renal excretion. Recommendations are given for dosage adjustment in patients with renal insufficiency.
Comparison of the Activity of Ionophores with Other Antibacterial Agents Against Anaerobes
Authors: Watanabe Kimihiro , Watanabe Junko , Kuramitsu Sayoko , Maruyama Hiromi B.
Published: June 2012

Representative polyethers of each group in Westley's classification and related ionophore antibiotics were examined for in vitro activity against 25 anaerobic strains. Lasalocid (X-537A) and nigericin were found to have activity comparable in potency to some leading antianaerobe antibiotics, newer cephalosporins and nitroimidazoles, with a different spectrum as revealed by a spectral comparison. A strict relationship between their antianaerobe activity and either their structural features or cation transporting properties was not apparent.
Cephamycin C treatment of induced swine salmonellosis
Authors: Jacks T M , Welter C J , Fitzgerald G R , Miller B M
Published: June 2012

Weanling pigs in groups of 12 were infected orally with Salmonella choleraesuis and were treated intramuscularly with doses of cephamycin C ranging from 12.5 to 337.5 mg twice daily for 10 days beginning 1 day postinoculation. Pigs in two other infected groups either received 300 mg of tetracycline orally on a similar schedule or served as nonmedicated controls. Optimal responses to cephamycin C were achieved at a twice daily dose of 112.5 mg. With this regimen, the febrile response was significantly reduced on day 2 and eliminated by day 5 postinfection, and the shedding of Salmonella spp. in feces was eliminated by day 5 postinfection; essentially, no lesions were found in the gastrointestinal tract at necropsy (day 26 postinfection). There was no mortality among recipients of the 112.5-mg dose; diarrhea was present on only 2% of the observation days. In contrast, 83% of the infected, nonmedicated pigs and 25% of the tetracycline-medicated pigs died, and diarrhea was present in these groups on 63 and 54% of the observation days, respectively. The striking benefits of cephamycin C treatment was achieved without adverse reactions. The weight gain and feed efficiency of the infected pigs treated with the 112.5-mg dose of cephamycin C and the noninfected, nonmedicated control pigs were equivalent.
Assays of serum aminoglycoside levels by BACTEC 460 in the presence of cefamandole and cefoxitin
Authors: Phillips L E , Martin R F , Luper W E , Rogers T E
Published: June 2012

The effects of cefamandole and cefoxitin on the assays of serum containing gentamicin, tobramycin, or amikacin by the BACTEC 460 (Johnston Laboratories, Cockeysville, Md.) were studied. The results were analyzed to determine whether the presence of the test substances, cefamandole or cefoxitin, caused a statistically different mean value of aminoglycoside or increase in variance as compared with serum assayed in their absence. The results were then considered in light of medical significance to see whether the difference observed would have any real effect on patient care. The results of each analyses dictate that serum of patients treated with both amikacin and cefamandole be tested in triplicate.
Outer Membrane Permeability Barrier Disruption by Polymyxin in Polymyxin-Susceptible and -Resistant
Salmonella typhimurium
Authors: Vaara Martti , Vaara Timo
Published: June 2012

In contrast to their polymyxin-susceptible parent strains, polymyxin-resistant
Salmonella typhimurium
mutants (
pmrA
strains) did not lose their outer membrane permeability barrier to macromolecules such as lysozyme and periplasmic proteins upon polymyxin treatment. The sensitization of
pmrA
strains to deoxycholate-induced lysis required 10-times-higher polymyxin concentrations than did the sensitization of the parent strains. These findings indicate that the
pmrA
mutation affects the outer membrane and decreases its susceptibility to polymyxin. By contrast, the
pmrA
mutants did not differ from their parents in the uptake of gentian violet after treatment with polymyxin, suggesting a degree of specificity in the
pmrA
effect in the outer membrane.
Antimicrobial susceptibility of Campylobacter jejuni with special reference to resistance patterns of Canadian isolates
Authors: Karmali M A , De Grandis S , Fleming P C
Published: June 2012

Agar dilution antimicrobial susceptibility testing of Camphylobacter jejuni showed that erythromycin, clindamycin, nitrofurantoin, and gentamicin were the most active compounds, inhibiting 90% of the isolates at a concentration of 1 microgram/ml or less. The frequency of high-level erythromycin resistance was 1%. Erythromycin-resistant isolates showed cross-resistance to clindamycin. All strains were inhibited by chloramphenicol at less than or equal to 8 micrograms/ml. About 20% of the isolates were resistant to tetracycline at 4 micrograms/ml. All strains were highly resistant to novobiocin, bacitracin, vancomycin, and trimethoprim and resistant to rifampin. The minimal inhibitory concentrations (MICs) of metronidazole ranged from less than or equal to 0.5 to 128 micrograms/ml. The susceptibility of strains to sulfamethoxazole and polymyxin B sulfate was markedly influenced by inoculum size. The MICs of polymyxin B sulfate were significantly higher at 42 than 36 degrees C. All strains were inhibited by nalidixic acid at 32 micrograms/ml. In the penicillin group, ampicillin was the most active compound, inhibiting only about three-quarters of the strains at 8 micrograms/ml. The cephalosporins as a group showed only moderate to poor activity, the most active cephalosporin being cefotaxime, which inhibited about 90% of the strains at 8 micrograms/ml. The use of antibiotics in selective media is discussed.
Single-dose pharmacokinetics of acyclovir
Authors: Spector S A , Connor J D , Hintz M , Quinn R P , Blum M R , Keeney R E
Published: June 2012

The pharmacokinetics of intravenously administered acyclovir were studied in 10 patients with advanced malignancies. After doses of 0.5 and 1.0 mg/kg, the slow disposition half-life values (t1/2beta) ranged from 2.2 to 3.1 h for the 1-h infusions and from 1.8 to 3.7 h for the 6-h infusions. Plasma levels, measured by radioimmunoassay, reached a maximum at the end of the 1-h infusions and approached steady state at 3 to 4 h into the 6-h infusions. Mean peak plasma concentrations obtained at 0.5 and 1.0 mg/kg administered over 1 h were 3.03 and 5.99 microM, respectively. Mean peak levels for the 6-h infusions were 1.07 microM at 0.5 mg/kg and 2.58 microM at 1.0 mg/kg. The mean urinary elimination of acyclovir was 44.7% of the administered doses. No clinical or laboratory abnormalities were noted in the 10 patients studied.