bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Titertek Multiskan for determining minimal inhibitory concentration endpoints
Authors: Genta V M , McCarthy L R , Herrick M , Rose F
Published: June 2012

A commercially available through-the-plate reading photometer (Titertek Multiskan, Flow Laboratories, McLean, Va.) was used to determine microdilution minimal inhibition concentrations (MICs) for 190 clinical isolates of bacteria (115 gram-negative rods and 75 gram-positive cocci). The performance of the instrument was evaluated by comparing its MIC readings to those that were visually determined. The MICs determined by the instrument were identical to those determined visually for 94% of the gram-negative rods and 89% of the gram-positive cocci tested. Of the MICs determined by the instrument, 99% was within one dilution of the MICs determined visually.
Pyridinium-2-azo-p-dimethylaniline chromophore, a new chromogenic cephalosporin for rapid beta-lactamase testing
Authors: Jorgensen J H , Crawford S A , Alexander G A
Published: June 2012

A new chromogenic cephalosporin, pyridinium-2-azo-p-dimethylaniline chromophore, was evaluated for use in a rapid paper strip or tube test for the detection of beta-lactamases from a variety of microorganisms. A 1-min pyridinium-2-azo-p-dimethylaniline chromophore paper strip test was found to be a convenient and accurate method for the detection of beta-lactamase-producing strains of Haemophilus influenzae and Neisseria gonorrhoeae, although it could not be relied upon to detect beta-lactamases produced by staphylococci, enteric organisms, or Bacteroides fragilis.
Inhibition of herpes simplex virus replication by methyl daunosamine
Authors: Spivack J G , Prusoff W H , Tritton T R
Published: June 2012

Methyl daunosamine inhibited the replication of herpes simplex virus type 1 in a dose-dependent manner. The growth of the host Vero cells was not affected by daunosamine levels that had significant antiviral activity (2.5 mM) but was inhibited by concentrations of 5 mM or greater. Methyl daunosamine appears to be unique among the sugars with antiviral activity because at antiviral concentrations it did not inhibit the glycosylation of macromolecules.
Randomized comparative study of moxalactam and cefazolin in the treatment of acute urinary tract infections in adults
Authors: Lea A S , Sudan A W , Wood B A , Gentry L O
Published: June 2012

Eighty-nine patients with clinical and laboratory evidence of acute urinary tract infection were randomized to therapy with either moxalactam (500 mg) or cefazolin (1 g) every 12 h. Escherichia coli was the predominant pathogen in both groups (92.6 versus 90.2%). Therapy was continued for 3 days after the patient defervesced. The minimum hospital stay was 5 days. Sequential urine cultures were obtained on day 3, at discharge, and 5 to 10 days after the cessation of therapy. THe average duration of hospital stay was 5.6 days for both groups of patients. THe incidence of recurrent infection was similar in uncomplicated patients (9.1 versus 10%) and in complicated patients with a condition predisposing them to urinary tract infections (43 versus 42%). Moxalactam-treated patients had a higher incidence of reversible hepatic enzyme elevation (36%) and Streptococcus faecalis superinfections (12.2%). Moxalactam is as effective as cefazolin for the elimination of gram-negative pathogens from the urine of patients with acute urinary tract infections, but it is associated with a higher incidence of reversible side effects.
Metabolism of Thienamycin and Related Carbapenem Antibiotics by the Renal Dipeptidase, Dehydropeptidase-I
Authors: Kropp Helmut , Sundelof Jon G. , Hajdu Richard , Kahan Frederick M.
Published: June 2012

Thienamycin (THM), the
N
-formimidoyl thienamycin derivative MK0787, and related carbapenem antibiotics were metabolized extensively in mice, rats, rabbits, dogs, rhesus monkeys, and chimpanzees. Urinary recovery of THM ranged from a low of 5% in dogs to 58% in rhesus monkeys. Renal clearance rates in dogs and chimpanzees were unusually low, less than glomerular filtration rates. The reduction in clearance of THM and MK0787 from plasma of rats and rabbits after ligation of renal arteries indicate that the kidneys are responsible for 35 and 92%, respectively, of metabolic drug clearance. Degradation was detected only in kidney homogenates. The enzyme activity was membrane bound and sensitive to inhibitors of Zn-metalloenzymes such as EDTA. A renal dipeptidase, dehydropeptidase-I (DHP-I), EC 3.4.13.11, was found to be responsible for the metabolism of the THM-class antibiotics, which exhibit a structural homology to dehydropeptides. A parallel increase in specific activity against THM and the substrate of DHP-I, glycyldehydrophenylalanine, was observed during solubilization and purification of the enzyme from porcine and human renal cortex. DHP-I was found to catalyze the hydrolysis of the beta-lactam ring in THM and MK0787. The products of the enzyme reaction were identical by high-powered liquid chromatography to their respective metabolites found in the urine. Nonbasic
N
-acylated THM and natural
N
-acylated carbapenems (epithienamycins and olivanic acids) were degraded 4- to 50-fold faster than THM when exposed to the enzymatic hydrolysis of DHP-I. Good correlations were obtained between the increased susceptibility of the carbapenem antibiotics to DHP-I as measured in the in vitro enzyme assay and the generally lower recoveries of active antibiotic in the urine of test animals. Despite this unusual degree of metabolism localized in the kidney, the plasma half-life of MK0787 and its efficacy against experimental systemic infections in animals remain satisfactory.
Rapidly growing mycobacteria: testing of susceptibility to 34 antimicrobial agents by broth microdilution
Authors: Swenson J M , Thornsberry C , Silcox V A
Published: June 2012

A total of 18 strains of Mycobacterium fortuitum, 15 strains of M. chelonei, and 31 strains of M. chelonei-like organisms were tested by both broth microdilution and agar dilution to determine their susceptibility to 34 antimicrobial agents. All strains grew well enough in cation-supplemented Mueller-Hinton broth for endpoints to be read after 72 h of incubation. Some strains of M. chelonei did not grow on Mueller-Hinton agar. A few discrepancies were noted between the broth and agar procedures. For M. fortuitum, doxycycline, minocycline, amikacin, sulfamethoxazole, and sulfamethoxazole-trimethoprim were the most active agents. For M. chelonei, amikacin, sisomicin, tobramycin, and erythromycin were the most active agents. The M. chelonei-like organisms were most susceptible to ampicillin, doxycycline, minocycline, amikacin, erythromycin, sulfamethoxazole, and sulfamethoxazole-trimethoprim. Broth microdilution appears to be a reliable method for susceptibility testing of rapidly growing mycobacteria, although clinical studies are needed to determine how well in vitro results correlate with therapeutic in vivo outcome.
Ribosomal resistance in the gentamicin producer organism Micromonospora purpurea
Authors: Piendl W , Böck A
Published: June 2012

The mechanism of resistance of the gentamicin-producing organism Micromonospora purpurea was analyzed. Determination of minimal inhibitory concentrations revealed high resistance to the 4,6-substituted deoxystreptamine aminoglycosides amikacin, gentamicin, kanamycin, netilmicin, sisomicin, and tobramycin and also to lividomycin A and hygromycin B, but susceptibility to streptomycin, dihydrostreptomycin, paromomycin, and neomycin during all phases of the growth cycle. The nonproducing, closely related Micromonospora melanosporea was susceptible to these compounds. In agreement with results from previous studies (R. Benveniste and J. Davies, Proc. Natl. Acad. Sci. U.S.A. 70:2276-2280, 1973), extracts from M. purpurea showed no activity of enzymes specifically modifying gentamicin. 70S ribosomes from M. purpurea but not from M. melanosporea were resistant to inhibition by gentamicin, kanamycin, tobramycin, and lividomycin in a polyuridylic acid-dependent polyphenylalanine synthesis system and susceptible to those compounds which were inhibitory in vivo. The former antibiotics were also unable to induce misreading. Subunit exchange experiments between M. purpurea and M. melanosporea showed that the main site for inhibition and induction of misreading is the 30S subunit (up to gentamicin concentrations of 10 micrograms/ml).
Dissociation of the inhibitory effects of 2-deoxy-D-glucose on Vero cell growth and the replication of herpes simplex virus
Authors: Spivack J G , Prusoff W H , Tritton T R
Published: June 2012

Vero cells treated for 24 h with a concentration of 2-deoxy-D-glucose (2dGlc) that inhibited the production of infectious herpes simplex virus type 1 grew at the same rate as untreated cells. Longer exposures to 2dGlc inhibited the growth of Vero cells in a dose-dependent manner, but without any loss of viability, and could be reversed by replating the cells in the absence of drug. To exhibit antiviral activity, 2dGlc had to be present during the replication cycle of herpes simplex virus type 1. Treatment of Vero cells, even with a cytotoxic dose of 2dGlc, was without effect on the yield of infectious virus, provided the drug was removed before infection. Thus the antiviral effects of 2dGlc were not the result of, and appeared to be independent of, persistent host cell toxicity.
Comparative in vitro activities of temocillin and cefazolin against Klebsiella pneumoniae
Authors: Lagast H , Klastersky J
Published: June 2012

Temocillin (BRL 17421) a new penicillin, was compared with cefazolin against 20 strains of Klebsiella. The in vitro minimal bactericidal concentration of cefazolin was twice as active as that of temocillin. Serum bactericidal levels obtained in volunteers treated with temocillin were consistently higher than those levels reached after the administration of cefazolin at the 6-h sampling.
In vitro comparison of clindamycin and pirlimycin (U-57930E) activity against Staphylococcus aureus
Authors: Evans M E , Patterson L S , Stratton C W
Published: June 2012

The activities of clindamycin and its derivative, pirlimycin (U-57930E), were compared against 100 strains of Staphylococcus aureus, using a microtiter broth dilution technique. Minimal inhibitory concentrations demonstrated that pirlimycin was comparable to clindamycin but offered no increase in activity against either methicillin-susceptible or methicillin-resistant S. aureus.
In vitro activity of pipecolic acid amide of clindamycin (U-57930E) on anaerobic bacteria compared with those of clindamycin, cefoxitin, and chloramphenicol
Authors: Dhawan V K , Bansal M B , Thadepalli H
Published: June 2012

In vitro activity of pipecolic acid amide of clindamycin (U-57930E) against 265 isolates of anaerobic bacteria, including 66 strains of Bacteroides fragilis, was compared with those of clindamycin, chloramphenicol, and cefoxitin. At therapeutically achievable concentrations, the activities of all four antibiotics against anaerobic bacteria were similar.
Action of antifungal imidazoles on Staphylococcus aureus
Authors: Sud I J , Feingold D S
Published: June 2012

In Staphylococcus aureus, using the imidazoles miconazole and ketoconazole, detailed studies of minimal inhibitory concentrations, kinetics of growth, viability, and release of intracellular K+ confirm that the two imidazoles work differently in this bacterium. Miconazole is bactericidal at low concentrations and causes release of cellular K+. Ketoconazole has no bactericidal effect at any tested concentration and has little effect on K+ permeability of S. aureus; it slows growth at high concentration. This is reflected in a low minimal inhibitory concentration for miconazole and a high one for ketoconazole. The probable mechanisms of the bacteriostatic and bactericidal effects of the imidazoles are discussed in light of these results and the previously described antifungal mechanisms of the drugs. alpha-Tocopherol blocks the action of both imidazoles.
Susceptibility to 5-fluorocytosine and prevalence of serotype in 402 Candida albicans isolates from the United States
Authors: Stiller R L , Bennett J E , Scholer H J , Wall M , Polak A , Stevens D A
Published: June 2012

Candida albicans isolates from 402 patients with no prior history of treatment with 5-fluorocytosine were collected at five medical centers from different areas of the United States. Isolates could be separated into four groups based on their minimum inhibitory concentrations (MICs) to 5-fluorocytosine. Group I isolates (60%) had MICs less than or equal to 12.5 micrograms/ml after 7 days, whereas groups II (22%), III (14%), and IV (4%) demonstrated MICs greater than 12.5 micrograms/ml on days 7, 2, and 1, respectively. Serotypes A and B accounted for 50.7 and 49.3%, respectively, of the 398 isolates typed. Serotype B was less prevalent in group I (26%), but predominated in the more resistant groups, groups II (85%), III (86%), and IV (53%). The common practice of identifying as "resistant" those isolates with MICs greater than 12.5 micrograms/ml after 48 h of incubation would yield a resistance rate in the United States of 11.5 to 15.5% in four centers and 35% in the fifth. Although serotype B and small agar disk diffusion zone sizes correlated with poor 5-fluorocytosine susceptibility, their ability to predict tube dilution MICs was limited. The true predictive value of such tests awaits correlation with in vivo studies.
Properties of a new penicillinase type produced by Bacteroides fragilis
Authors: Sato K , Matsuura Y , Inoue M , Mitsuhashi S
Published: June 2012

A highly penicillin-resistant strain of Bacteroides fragilis, strain GN11499, was found among 80 clinical isolates of the B.fragilis group and appears to produce a new type of penicillinase. Penicillinase activity was detected in crude extracts and had a specific activity of 0.25 U/mg of protein. About 20% of the enzyme was released into the surrounding medium during growth. The enzyme hydrolyzed ampicillin and cloxacillin more rapidly than it did penicillin G, carbenicillin, and cephaloridine. Relative rates in a crude extract with penicillin G as 100 were ampicillin, 357; carbenicillin, 57; cloxacillin, 271; and cephaloridine, 71. Enzyme activity was inhibited by clavulanic acid, CP-45, 899, N-formimidoyl thienamycin, cefoxitin, moxalactam, and p-chloromercuribenzoate. The enzyme had a molecular weight of approximately 41,500 and an isoelectric point of 6.9. Penicillinase production and tetracycline resistance were transferred from B.fragilis GN11499 to two susceptible strains of B.fragilis and Bacteroides vulgatus by filter mating.
In vitro susceptibility and cross-resistance of South African isolates of Neisseria gonorrhoeae to 14 antimicrobial agents
Authors: Liebowitz L D , Ballard R C , Koornhof H J
Published: June 2012

One hundred isolates of Neisseria gonorrhoeae obtained from patients attending clinics in Johannesburg, South Africa, were tested by a broth dilution technique for their minimal inhibitory concentrations (MICs) of benzyl penicillin G, ampicillin, cefoxitin, cefuroxime, cefotaxime, ceftriaxone, ceftazidime, tetracycline, minocycline, doxycycline, spectinomycin, rosaramicin, chloramphenicol, and rosoxacin. None of the isolates tested produced beta-lactamase. The MICs of penicillin ranged from less than or equal to 0.007 to 0.5 micrograms/ml. The isolates were also very susceptible to rosaramicin (minimal concentration at which 50% of isolates were inhibited [MIC50] = 0.02 micrograms/ml) and to the new cephalosporins (cefotaxime MIC50 less than 0.007 micrograms/ml, ceftriaxone MIC50 less than 0.007 micrograms/ml, and ceftazidime MIC50 less than 0.007 micrograms/ml). By using regression analysis, good correlation was observed between the MICs of penicillin and those of the other agents, with the exception of ceftriaxone, spectinomycin, and rosaramicin. The MICs and the minimal bactericidal concentrations were within a log2 concentration of each other.
Direct and specific inactivation of rhinovirus by chalcone Ro 09-0410
Authors: Ishitsuka H , Ninomiya Y T , Ohsawa C , Fujiu M , Suhara Y
Published: June 2012

Studies of various analogs related to the antipicornavirus agent, 4',5-dihydroxy-3,3',7-trimethoxyflavone (Ro 09-0179), led to the identification of 4'-ethoxy-2'-hydroxy-4,6'-dimethoxychalcone (Ro 09-0410), a new and different type of antiviral agent. Ro 09-0410 had a high activity against rhinoviruses but no activity against other picornaviruses. Of 53 rhinovirus serotypes so far tested, 46 were susceptible to Ro 09-0410 in HeLa cell cultures. The concentration of Ro 09-0410 inhibiting 50% of the types of rhinovirus was about 0.03 micrograms/ml, whereas the 50% cytotoxic concentration was 30 microgram/ml. Ro 09-0410 inactivated rhinoviruses in direct dose-, time-, and temperature-dependent fashion. Since infectivity, reduced by exposure to the agent, completely regained the original level by extraction of the agent with chloroform, the inactivation may be associated with the binding of the agent to some specific site of the rhinovirus capsid.
Concentrations of cefoxitin in gallbladder bile of cholecystectomy patients
Authors: Hansbrough J F , Clark J E
Published: June 2012

Cefoxitin was administered in a dose of 2 g intravenously to 17 patients scheduled for cholecystectomy. The concentrations of this agent in serum and gallbladder bile were measured simultaneously upon opening of the abdominal cavity. Concentrations of cefoxitin in excess of 10 microgram/ml were present in the gallbladder bile of 12 of the 13 patients from samples obtained between 35 and 165 min after cefoxitin infusion. Cystic or common duct obstruction did not preclude entry of the drug into gallbladder bile.
Mechanism of action of dnacin B1, a new benzoquinoid antibiotic with antitumor properties
Authors: Tanida S , Hasegawa T , Yoneda M
Published: June 2012

Dnacin B1 preferentially inhibited the incorporation of [3H]thymidine into acid-insoluble fractions in Escherichia coli. At a sublethal concentration, dnacin B1 caused filamentous growth in E. coli and induced prophage lambda. The antibiotic also showed potent bactericidal activity against repair-deficient E. coli strains, such as recA, recB, and polA strains, In in vitro studies, dnacin Ba raised the melting temperatures of various double-stranded DNAs. In addition, the antibiotic showed DNA-cleaving activity against PM2 DNA in the presence of reducing agents, and the activity was suppressed by scavengers for oxygen free radicals and an iron-specific chelator, desferrioxamine E. The stimulation of the generation of superoxide radical by dnacin B1 was confirmed by measuring the reduction of neotetrazolium. Therefore, it can be presumed that the primary cellular target of dnacin B1 is DNA in susceptible cells, and the autooxidation of DNA-bound dnacin B1 causes the generation of oxygen-free radicals that result in the damage of DNA and the inhibition of its synthesis.
Diffusion of beta-lactam antibiotics through liposome membranes containing purified porins
Authors: Kobayashi Y , Takahashi I , Nakae T
Published: June 2012

A method to determine the diffusion of cephalosporins through porin pores in vitro was developed, using liposomes reconstituted from phospholipids, lipopolysaccharides, and purified porin trimers. With this method, the roles of several species of porin pores from Escherichia coli and Salmonella typhimurium in the diffusion of cephalexin, cephaloridine, and cephalothin were examined. Results clearly showed that porins from E. coli B and 39,000-molecular-weight porins from S. typhimurium formed the most efficient pores. Thus, these were considered to represent a single functional group. OmpF and OmpE porins of E. coli K-12 and 38,000-molecular-weight porins of S. typhimurium formed moderately efficient pores. OmpC porins of E. coli K-12 and 40,000-molecular-weight porins of S. typhimurium were the least efficient pore formers. The present method can be used to distinguish the role of individual porin pores in the diffusion of cephalosporins.
High-pressure liquid chromatographic method for determination of Sch 29482 in human serum
Authors: Kim H , Oden E , Lin C
Published: June 2012

A high-pressure liquid chromatographic method was developed for quantitative determination in human serum of a new penem antibiotic known as Sch 29482 (5R,6S,8R-2-ethylthio-6(1-hydroxyethyl)penem-3-carboxylic acid). The method involves serum extraction at an acid pH with ether, followed by separation on a reverse-phase column and UV light detection at 254 nm. This technique produced a good linear relationship between the peak height ratio and the Sch 29482 concentration, which ranged from 0.09 to 35.64 micrograms/ml. In addition, this procedure proved to be quite specific for Sch 29482, since all beta-lactam antibiotics tested did not interfere with the assay. For high concentrations (greater than 0.5 micrograms/ml), the mean values obtained from the high-pressure liquid chromatographic method correlated very well (r = 0.997) with those obtained from a microbiological assay. This method is accurate and reproducible, with a sensitivity of about 0.09 micrograms per ml of serum. It is useful for monitoring serum drug levels in animals and humans and can also be used for drug pharmacokinetic studies in humans.
Cefotetan, a new cephamycin: comparison of in vitro antimicrobial activity with other cephems, beta-lactamase stability, and preliminary recommendations for disk diffusion testing
Authors: Ayers L W , Jones R N , Barry A L , Thornsberry C , Fuchs P C , Gavan T L , Gerlach E H , Sommers H M
Published: June 2012

Cefotetan is a new, potent, 7 alpha-methoxy cephalosporin (cephamycin). The in vitro activity of cefotetan tested in a multiphasic, collaborative study against 12,260 consecutive clinical isolates and 448 selected isolates showed 93% of Enterobacteriaceae, 90% of methicillin-susceptible Staphylococcus aureus (broth dilution), 83% of Bacteroides fragilis, and 72% of non-enterococcal streptococci to be inhibited by less than or equal to 8 micrograms/ml. Beta-Lactamase-producing and -nonproducing Haemophilus influenzae strains were inhibited by less than or equal to 1.0 micrograms/ml. Cefotetan's inhibitory spectrum paralleled those of the newest generation of cephems and exceeded those of cefoxitin and cefamandole. No useful activity was present against Streptococcus faecalis or Pseudomonas aeruginosa. Cefotetan was bactericidal without significant inoculum effect and was highly resistant to hydrolysis by Richmond-Sykes types I, III, and IV beta-lactamases. Hydrolysis of the chromogenic cephalosporin PADAC (pyridine-2-azo-p-dimethylaniline cephalosporin) by type I beta-lactamases was markedly inhibited by concentrations of cefotetan similar to those of the potent inhibitor dicloxacillin. Analysis of agar disk diffusion for several disk potencies and broth dilution susceptibility tests by regression and error rate-bounding methods produced preliminary tentative zone standards (30-micrograms disk, using minimal inhibitory concentration breakpoints of less than or equal to 8 micrograms/ml susceptible and greater than 32 micrograms/ml resistant, or 75-micrograms disk, using minimal inhibitory concentration breakpoints of less than or equal to 16 micrograms/ml susceptible and greater than or equal to 64 micrograms/ml resistant) of greater than or equal to 18 mm susceptible, less than or equal to 14 mm resistant, and 15 to 17 mm indeterminate. Staphylococcus aureus testing with the 30-micrograms disk is not recommended.
Susceptibility of group B streptococci to 16 beta-lactam antibiotics, including new penicillin and cephalosporin derivatives
Authors: Jacobs M R , Kelly F , Speck W T
Published: June 2012

The susceptibility of 100 group B streptococci to 16 beta-lactam antibiotics was tested by agar dilution. Penicillin G and N-formimidoyl thienamycin were the most active agents tested, both having a 90% minimal inhibitory concentration (MIC90) of 0.06 microgram/ml. Ceftriaxone, cefotaxime, cefamandole, and SCH 29482 were almost as active, all having an MIC90 of 0.12 microgram/ml, and ampicillin, cephalothin, and mezlocillin all had an MIC90 of 0.25 microgram/ml. The MIC90 for piperacillin, cefoperazone, and ceftazidime was 0.5 microgram/ml. Least active were carbenicillin, ticarcillin, cefoxitin, and moxalactam, with MIC90s of 1, 2, 4, and 8 micrograms/ml, respectively. No penicillin-tolerant strains were detected.
Susceptibility of Haemophilus influenzae type b to cefaclor and influence of inoculum size
Authors: Levin R M , Azimi P H , Dunphy M G
Published: June 2012

Cefaclor appeared to be an effective antibiotic against both beta-lactamase-positive and beta-lactamase-negative strains of Haemophilus influenzae type b when tested with 10(5) colony-forming units per ml. With inocula in excess of 10(6) colony-forming units per ml, these organisms were neither inhibited nor killed at concentrations of 400 micrograms/ml. This inoculum effect was also demonstrated in time-kill curve studies.
Synergism among BIOLF-62, phosphonoformate, and other antiherpetic compounds
Authors: Smith K O , Galloway K S , Ogilvie K K , Cheriyan U O
Published: June 2012

9-[[2-Hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine (BIOLF-62) is highly synergistic with either phosphonoformate or phosphonoacetate when used in combination against herpes simplex virus types 1 and 2 in vitro. Acycloguanosine did not show significant synergism with these two compounds. Bromovinyldeoxyuridine and phosphonoformate were highly synergistic against herpes simplex virus type 2, but not against type 1.
In Vitro Evaluation of
N
-Formimidoyl Thienamycin (MK0787) Combined with Amikacin Against Gram-Negative Bacilli and
Staphylococcus aureus
Authors: Enciso M. Díez , Lindemann M. L. Mateos , Altés A. Gutiérrez
Published: June 2012

The in vitro synergistic activity of
N
-formimidoyl thienamycin and amikacin was determined against gentamicin-resistant enterobacteriaceae,
Pseudomonas aeruginosa
, and
Staphylococcus aureus. N
-Formimidoyl thienamycin showed synergism with amikacin against 19 of the gentamicin-resistant strains, 14 of the 49 strains of
S. aureus
, and only 1 strain of the 46
P. aeruginosa
isolates.
Cefamandole bile levels in patients with hepatobiliary disease
Authors: Uwaydah M , Kantarjian H , Osseiran M , Bal'a F
Published: June 2012

Intraoperative biliary cefamandole concentrations were determined in 16 patients with hepatobiliary pathology. These included seven patients with cholelithiasis, five with acute cholecystitis, two with recurrent ascending cholangitis, and two with liver abscesses. Bile collected 0.5 to 2.5 h after the last antibiotic dose of 1 g administered by intravenous drip showed therapeutically effective concentrations of cefamandole in 84% (11 of 13) of gall bladder samples with a median of 220 micrograms/ml (range, 1.6 to 1,400), and in 100% (13 of 13) of common bile duct samples with a median of 1,100 micrograms/ml (range, 9.0 to greater than 2,000). Only with complete aseptic cystic duct obstruction was cefamandole undetectable in gall bladder bile.
Pharmacokinetics of cefotetan (YM09330) in humans
Authors: Nakagawa K , Koyama M , Tachibana A , Komiya M , Kikuchi Y , Yano K
Published: June 2012

The pharmacokinetics and safety of cefotetan (YM09330) were examined after intravenous administration of single and multiple doses to normal volunteers. Cefotetan was well tolerated in single doses of 500 to 3,000 mg and in multiple doses of 500 and 1,000 mg at 12-h intervals for 1 and 3 days. These doses produced high plasma levels. The half-life (3 h) of cefotetan was longer than that of cefazolin. There was no evidence of drug accumulation in the plasma in the multiple-dose study. Mean recoveries of cefotetan in urine within a 24-h period were 74.5 to 88.4% of the dose, regardless of the route of administration and the dosage. The tautomer of cefotetan accounted for approximately 5% of the dose excreted in the urine. No tautomer was detected in plasma. Concentrations of drug in plasma and urine measured by microbiological assay were in good agreement with those measured by high-pressure liquid chromatography.
Role of porin proteins OmpF and OmpC in the permeation of beta-lactams
Authors: Jaffe A , Chabbert Y A , Semonin O
Published: June 2012

Mutants of Escherichia coli K-12 lacking major outer membrane proteins were obtained by selecting for resistance to the beta-lactam cefoxitin. Three classes of resistant strains were found: mutants in ompB, a regulatory locus for proteins OmpF and OmpC; mutants in ompF; and one mutant in tpo. The OmpF and OmpC proteins facilitate penetration of beta-lactams through the outer membrane.
Simultaneous comparison of three methods for assessing ceftazidime penetration into extravascular fluid
Authors: Ryan D M , Hodges B , Spencer G R , Harding S M
Published: June 2012

The penetration of ceftazidime, a new broad-spectrum cephalosporin, into fluids from subcutaneous threads, suction blisters, and cantharidin blisters was studied in eight healthy male volunteers. A pharmacokinetic analysis showed fundamental differences between the models. The results obtained with the subcutaneous thread technique were similar to those of the peripheral compartment and were characteristic of a rapidly equilibrating compartment. The results obtained with the suction and cantharidin blister techniques were characteristic of slowly equilibrating compartments. We concluded that although one model will not accurately predict the penetration of an antibiotic in all clinical situations, each model will have its own particular application.
Inhibition of human cytomegalovirus by trifluorothymidine
Authors: Spector S A , Tyndall M , Kelley E
Published: June 2012

The antiviral activity of trifluorothymidine (TFT) singly and in combination with other antiviral agents against human cytomegalovirus (HCMV) was evaluated by using an infectious center plaque reduction assay. The 50% inhibitory dose of TFT against six different patient HCMV strains was 0.57 (+/- 0.24, standard deviation) microM and ranged from 0.32 to 0.97 microM. The 50% inhibitory dose for the laboratory-adapted HCMV strain, AD-169, was 2.1 microM. When TFT (0.17 microM) was combined with human fibroblast interferon (25 U/ml), the combination was additive against all four HCMV isolates evaluated. Synergism was observed when TFT (0.17 microM) was combined with phosphonoformic acid (25 microM) for all strains studied or with acyclovir (20 microM) for three of the four clinical HCMV strains tested. Each of the three antiviral agents, when combined with TFT, exhibited additive effects against strain AD-169. TFT at concentrations of 0.5, 1.7, and 3.5 microM had an increasing inhibitory effect on uninfected human embryonic lung fibroblast (HEL) cell growth over 72 h, with 16% growth inhibition at 3.5 microM after 3 days. There was no increased toxicity to growing HEL cells when the paired antiviral agent combinations were evaluated. These findings suggest that TFT may be useful singly or in combination with other antiviral agents in treating HCMV infections.
Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981
Authors: Farber B F , Moellering R C
Published: June 2012

A retrospective chart review of 98 patients treated with 100 courses of intravenous vancomycin was undertaken to better define its toxicity. Most of the patients carried diagnoses of Staphylococcus aureus or Staphylococcus epidermidis infection. Auditory toxicity was not seen, and fever and rash occurred in only 1 to 3% of the subjects. Phlebitis was noted in 13% of the cases and required discontinuation of therapy in 2%. Therapy was complicated by neutropenia (polymorphonuclear leukocyte count, less than or equal to 1,000 cells per cm3) in 2% of the patients but was rapidly reversible. Nephrotoxicity was uncommon (5%) and reversible in subjects receiving vancomycin alone, even when the therapy was continued. However, 35% of the patients receiving vancomycin with an aminoglycoside developed significant elevations in serum creatinine. Although this high incidence may have been due to the patient population selected or to the aminoglycoside therapy alone, the possibility of additive toxicity between vancomycin and the aminoglycosides should be considered.
Susceptibility of Pseudomonas paucimobilis to 24 antimicrobial agents
Authors: Smalley D L , Hansen V R , Baselski V S
Published: June 2012

Pseudomonas paucimobilis (group IIK, biotype 1) clinical isolates showed in vitro resistance to ampicillin, carbenicillin, cephalothin, cefoxitin, cefamandole, moxalactam, cefotaxime, cefoperazone, mezlocillin, azlocillin, piperacillin, and ticarcillin. Those agents to which the microbes were shown to be susceptible were tetracycline, chloramphenicol, gentamicin, tobramycin, kanamycin, amikacin, netilmicin, sisomicin, trimethoprim-sulfamethoxazole, ceftazidime, ceftriaxone, and ceftizoxime.
Comparative in vitro and in vivo activity of temocillin (BRL 17421) and ampicillin against Haemophilus influenzae type b
Authors: Yogev R , Glogowski W , Connor E
Published: June 2012

A total of 42 strains of Haemophilus influenzae type b isolated from pediatric patients were sensitive in vitro to temocillin (90% minimal inhibitory concentration = 0.25 microgram/ml). No difference in mean minimal inhibitory concentration between beta-lactamase producer (0.25 microgram/ml) and nonproducer (0.23 microgram/ml) strains was found. Various dosages of ampicillin or temocillin for the treatment of infant rats with ampicillin-resistant H. influenzae bacteremia and meningitis yielded no difference in cure rates. These results suggest that temocillin may not be as effective as other new cephalosporins for the treatment of H. influenzae type b infections.
Therapy of staphylococcal infections with cefamandole or vancomycin alone or with a combination of cefamandole and tobramycin
Authors: Coppens L , Hanson B , Klastersky J
Published: June 2012

Eighty adult patients with microbiologically demonstrated staphylococcal infections were included in a comparative trial of cefamandole and cefamandole plus tobramycin. Patients with cefamandole-resistant pathogens were treated with vancomycin, if the initial therapy consisted of cefamandole, but were continued on cefamandole plus tobramycin if already started on that combination. Of the patients infected with cefamandole-susceptible strains, 91% (20/22) responded favorably to treatment with cefamandole alone, and 88% (30/34) responded favorably to cefamandole plus tobramycin. Of the patients infected with cefamandole-resistant staphylococci, 70% (7/10) responded to treatment with cefamandole plus tobramycin, and 86% (12/14) responded to treatment with vancomycin, even though vancomycin therapy was started 24 to 48 h later than cefamandole-plus-tobramycin therapy. No major side effects were observed; however, cefamandole plus tobramycin was associated with a rise in the serum creatinine level in 11% (4/44) of the patients. The bactericidal activity of the serum in cefamandole-treated patients and in cefamandole-plus-tobramycin-treated patients was identical against cefamandole-susceptible strains. Against cefamandole-resistant strains, 87% of the vancomycin-containing sera were bactericidal at a dilution of 1:8, whereas only 57% of the cefamandole-plus-tobramycin-containing sera were active at that dilution.
Aminoglycoside accumulation kinetics in rat renal parenchyma
Authors: Aronoff G R , Pottratz S T , Brier M E , Walker N E , Fineberg N S , Glant M D , Luft F C
Published: June 2012

To test the hypotheses that the renal parenchymal accumulation kinetics of aminoglycosides can predict nephrotoxicity, we measured renal parenchymal concentrations in rats receiving gentamicin and tobramycin. In addition to comparing the drugs as single daily injections, we also examined the effect of multiple doses versus a single daily dose. Gentamicin accumulated to much greater concentrations in the kidney than did tobramycin. Gentamicin given twice daily accumulated more rapidly and to greater concentrations than did the same total dose given once daily. We conclude that aminoglycoside accumulation in the kidney depends on the drug and dose regimen. These differences may explain relative nephrotoxicities.
Characterization of beta-lactamase induction in Enterobacter cloacae
Authors: Gootz T D , Sanders C C
Published: June 2012

The induction of beta-lactamase was studied in a strain of Enterobacter cloacae. A wide variety of beta-lactam compounds were found to induce beta-lactamase in this organism, and the degree of induction was directly related to the stability of the inducer to degradation by the enzyme. The kinetics of the induction process were consistent with a system normally under repressor control, suggesting a direct interaction of the beta-lactam compound with a repressor protein in the E. cloacae cells. Although these characteristics are common to many inducible systems in gram-negative organisms, the induction of beta-lactamase in this strain was not subject to catabolite repression with glucose and remained unaffected by exogenous cyclic AMP in the culture medium. This suggests that the organization and function of the beta-lactamase regulatory genes in E. cloacae are unlike those of other inducible gene systems, such as those composing the well-characterized lactose operon in Escherichia coli.
Pharmacokinetics of Ceftriaxone in Pediatric Patients With Meningitis
Authors: Steele Russell W. , Eyre Linda B. , Bradsher Robert W. , Weinfeld Robert E. , Patel Indravadan H. , Spicehandler Jonathan
Published: June 2012

Pharmacokinetics of ceftriaxone after a single dose of 50 or 75 mg/kg were determined in 30 pediatric patients with bacterial meningitis. Data for doses of 50 and 75 mg/kg, respectively, were as follows (mean ± standard deviation): maximum plasma concentrations, 230 ± 64 and 295 ± 76 μg/ml; elimination rate constant, 0.14 ± 0.06 and 0.14 ± 0.04 h
−1
; harmonic elimination half-life, 5.8 ± 2.8 and 5.4 ± 2.1 h; plasma clearance, 51 ± 24 and 55 ± 18 ml/h per kg; volume of distribution, 382 ± 129 and 387 ± 56 ml/kg; mean concentration in cerebrospinal fluid 1 to 6 h after infusion, 5.4 and 6.4 μg/ml. A dosage schedule of 50 mg/kg every 12 h for bacterial meningitis caused by susceptible organisms is suggested for pediatric patients over 7 days of age.
Preparation and DNA-binding properties of substituted triostin antibiotics
Authors: Cornish A , Fox K R , Waring M J
Published: June 2012

Novel derivatives of the triostin group of antibiotics were prepared by supplementing cultures of the producing organism Streptomyces triostinicus with a variety of aromatic carboxylic acids. Five new antibiotics, each having both the natural quinoxaline chromophores replaced by a substituted ring system, were purified to homogeneity and characterized by high-pressure liquid chromatography and nuclear magnetic resonance. Their antibacterial activities and DNA-binding properties were investigated. Addition of a halogen atom at position 6 of the quinoxaline ring or an amino group at position 3 had little effect on either the biological activity or the DNA-binding characteristics. The bis-3-amino derivative is fluorescent, and its fluorescence is strongly quenched by calf thymus DNA and polydeoxyguanylate-polydeoxycytidylate but not by polydeoxyadenylate-polydeoxythymidylate, suggesting that it binds preferentially to guanosine-cytosine-rich sequences in natural DNA. Binding constants for the bis-6-chloro and bis-3-amino derivatives do not differ greatly from those of unsubstituted triostin A. The analogs having two quinoline chromophores or a chlorine atom in position 7 of the quinoxaline ring display little or no detectable antibacterial activity, in marked contrast to the other congeners. Bis-7-chloro-triostin A binds conspicuously more tightly to polydeoxyadenylate-polydeoxythymidylate than to any other polynucleotide tested.
Synergistic Effect of
N
-Formimidoyl Thienamycin with Gentamicin and Amikacin Against
Streptococcus faecalis
Authors: Gombert Myles E. , Berkowitz Leonard B. , Cummings Marinella C.
Published: June 2012

The in vitro activities of
N
-formimidoyl thienamycin alone and in combination with amikacin and gentamicin were tested against 10 strains of
Streptococcus faecalis
. Synergy was demonstrated in 35% of the combinations tested by the microtiter checkerboard technique; 50% were found to be synergistic with time killing curves.
Susceptibility of Nocardia asteroides to 46 antibiotics, including 22 beta-lactams
Authors: Gutmann L , Goldstein F W , Kitzis M D , Hautefort B , Darmon C , Acar J F
Published: June 2012

Twelve Nocardia asteroides isolates were tested for their susceptibility to 46 antibiotics by the agar dilution method. N-Formimidoyl thienamycin was the most active of 22 beta-lactam antibiotics, inhibiting 11 of the 12 strains at 1 microgram/ml. Penicillins, including ureidopenicillins, showed poor activity. Cefotaxime, ceftriaxone, and especially cefuroxime had the best activities of the cephalosporins tested. Among the other antibiotics, amikacin and minocycline, respectively, inhibited all of the strains tested at 0.5 and 4 micrograms/ml.
Single-dose pharmacokinetics of intravenous clavulanic acid with amoxicillin in pediatric patients
Authors: Schaad U B , Casey P A , Cooper D L
Published: June 2012

Pharmacokinetics of a parenteral formulation comprised of 5 parts of amoxicillin and 1 part of clavulanic acid were determined in 12 pediatric patients, 2 to 14 years of age. A single dose amounting to 25 mg of amoxicillin and 5 mg of clavulanic acid per kg of body weight was infused intravenously over 2 min. Mean plasma concentrations 5 min after dosing were 89.4 micrograms of amoxicillin per ml and 19.5 micrograms of clavulanic acid per ml. Terminal phase plasma half-lives were 1.2 and 0.8 h, respectively. The data acquired in this study indicate that amoxicillin and clavulanic acid are pharmacokinetically compatible. Moreover, taken with assessment of microbiological activities by others, the present data suggest that intravenous administration of 25 mg of amoxicillin plus 5 mg of clavulanic acid per kg every 6 h is a reasonable starting regimen for assessing the activity of the combined drug formulation in noninvasive childhood diseases caused by Haemophilus influenzae, Staphylococcus aureus, Streptococci spp., Neisseria spp., Branhamella catarrhalis, and other susceptible organisms.
Genetic transfer of antimicrobial resistance and enterotoxigenicity among Escherichia coli strains
Authors: Wachsmuth K , DeBoy J , Birkness K , Sack D , Wells J
Published: June 2012

To understand the role of enterotoxin (Ent) plasmids in epidemics of enterotoxigenic (ET) Escherichia coli diarrhea in the United States, we studied the genetics of Ent plasmids in relation to E. coli serotypes and R plasmids. Twenty-nine ET E. coli strains, including all epidemic isolates available at the Centers for Disease Control, Atlanta, Ga. (CDC), were assessed for the ability to transfer antimicrobial resistances (if present) by conjugation, to mobilize a nonconjugative R plasmid, and to cotransfer enterotoxigenicity with R determinants. Of the 12 ET E. coli strains isolated in the United States, 5 were able to transfer R plasmids; one strain cotransferred detectable enterotoxigenicity. Another four U.S. isolates were able to mobilize plasmid DNA, but no toxin production was detected in transconjugants. Of 17 resistant ET E. coli from South Asia, 13 were able to transfer R plasmids; 5 of those 13 cotransferred detectable Ent plasmids. In all, 22 ET E. coli strains (76%) were able to initiate conjugation and genetic transfers. Six of these strains (20%) were able to cotransfer enterotoxigenicity with a conjugative R plasmid at a detectable frequency. One of the six strains transferred R and Ent determinants on a single plasmid. These data are addressed in relation to the observed immobility of Ent and R during outbreaks of ET E. coli, the efficacy of prophylactic tetracycline, and the worldwide occurrence of a limited number of ET E. coli serotypes.
Norfloxacin disposition after sequentially increasing oral doses
Authors: Swanson B N , Boppana V K , Vlasses P H , Rotmensch H H , Ferguson R K
Published: June 2012

Single doses of norfloxacin (200, 400, 800, 1,200, and 1,600 mg) or placebo were administered orally at weekly intervals to 14 healthy male volunteers in a double-blind study. Norfloxacin was measured in serum and urine by high-pressure liquid chromatography with UV detection. The concentrations of this drug in serum peaked 1 to 2 h after each dose; the mean peak values for increasing doses were 0.75, 1.58, 2.41, 3.15, and 3.87 micrograms/ml. Mean area under the serum concentration-time curves for the first 12 h after each dose were 3.56, 6.26, 11.4, 16.1, and 19.7 micrograms . h/ml, respectively. The elimination half-life of norfloxacin was about 7 h and was similar for all doses. The concentrations of the drug in urine also peaked 1 to 2 h after dosage; mean peak values for increasing doses were 200, 478, 697, 992, and 1,045 micrograms/ml. Renal clearances approximated 285 ml/min. About 30% of each dose was excreted into urine as unmetabolized norfloxacin. Crystals of the drug were occasionally observed during microscopic examination of freshly voided urine collected after the 1,200- and 1,600-mg doses. Crystalluria was not encountered at lower doses.
Pharmacokinetics and tolerance of N-formimidoyl thienamycin (MK0787) in humans
Authors: Norrby S R , Alestig K , Ferber F , Huber J L , Jones K H , Kahan F M , Meisinger M A , Rogers J D
Published: June 2012

The pharmacokinetics of intravenously administered N-formimidoyl thienamycin (MK0787) were studied in 14 healthy male subjects in a single-dose study, in which the volunteers received N-formimidoyl thienamycin with and without probenecid, and in a multiple-dose study, in which the subjects were given 250 or 500 mg every 8 h for 10 doses. High dose-related plasma concentrations of N-formimidoyl thienamycin were achieved; co-administration with probenecid resulted in only minor increases in these concentrations. No accumulation in plasma was seen after multiple doses. The plasma half-life of N-formimidoyl thienamycin was slightly less than 1 h and did not increase significantly with the coadministration of probenecid. The urinary recovery of N-formimidoyl thienamycin varied between 6.0 and 38.4% of the dose with a marked intersubject variability. Variations in individual subjects were small, however, when the urinary recoveries after repeated doses were compared. These results were in agreement with previous animal studies showing a renal metabolism of N-formimidoyl thienamycin. Probenecid administration resulted in a marked decrease in N-formimidoyl thienamycin urinary recovery. In vitro experiments showed that the decay of N-formimidoyl thienamycin in spiked pretreatment urine samples was 2 to 5%/h with more rapid degradation at acidic than at basic pH.
Susceptibility of
Propionibacterium acnes
Clinical Isolates to 22 Antimicrobial Agents
Authors: Denys Gerald A. , Jerris Robert C. , Swenson Jana M. , Thornsberry Clyde
Published: June 2012

Susceptibilities of 104
Propionibacterium acnes
isolates to each of 22 antimicrobial agents was evaluated by broth microdilution. These isolates were susceptible to all of the test agents except metronidazole.
N
-Formimidoyl thienamycin, a penem coded Sch 29482, and penicillin ranked first, second, and third, respectively, in activity and were significantly more active than other penicillins, cephalosporins, tetracyclines, clindamycin, or chloramphenicol.