bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening of Neisseria gonorrhoeae for tolerant response to beta-lactam antibiotics
Authors: de Repentigny L , Turgeon P L
Published: June 2012

Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of penicillin, ampicillin, cefoxitin, and cefuroxime were determined for 103 beta-lactamase-negative Neisseria gonorrhoeae clinical isolates belonging to five different auxotypes. MBC determinations were base on killing 99.9% of the inoculum after 24 h of incubation. The MBC/MIC ratio was less than or equal to 8 for ampicillin, cefoxitin, and cefuroxime in all 103 strains. Two isolates which were very susceptible to penicillin (MIC, less than or equal to 0.015 micrograms/ml) had MBCs which were considerably greater than the MICs (MBC/MIC ratios, 32 and 64) for penicillin. A beta-lactamase-negative resistant subpopulation having the same auxotype as the total population was isolated from each of these two strains. Killing curve studies were in agreement with the existence of susceptible and resistant subpopulations, which may explain the high MBC/MIC ratios.
Involvement of the outer membrane in gentamicin and streptomycin uptake and killing in Pseudomonas aeruginosa
Authors: Hancock R E , Raffle V J , Nicas T I
Published: June 2012

Induction of a major outer membrane protein, H1, in Pseudomonas aeruginosa resulted in decreased susceptibility to gentamicin and streptomycin. Mutants which overproduce protein H1 and cells in which H1 is induced in response to growth conditions had altered kinetics of uptake and killing. It was further demonstrated that gentamicin and streptomycin interact with the outer membrane to permeabilize it to lysozyme and to increase the permeation of a chromogenic beta-lactam, nitrocefin. Experiments with inhibitors of aminoglycoside uptake showed that uptake was not required to increase permeability. Mg2+ at 1 mM totally inhibited aminoglycoside-mediated outer membrane permeabilization. We propose that the uptake and killing by these aminoglycosides requires interaction with an Mg2+ binding site at the outer membrane, permitting aminoglycoside uptake into the periplasm.
Comparative nephrotoxicity of gentamicin and tobramycin: pharmacokinetic and clinical studies in 201 patients
Authors: Schentag J J , Plaut M E , Cerra F B
Published: June 2012

A total of 201 critically ill patients were studied during 267 courses of gentamicin or tobramycin treatment (139 gentamicin courses and 128 tobramycin courses). Of these 267 courses, pharmacokinetic and clinical data were obtained for 240 (120 gentamicin and 120 tobramycin). The data collected for pharmacokinetic analysis included measurements of serial blood and urine levels, urinary excretion of beta 2-microglobulin, protein levels, and granular casts. A two-compartment model was used to assess tissue accumulation, and in 89 courses the predicted accumulation was confirmed by cumulative urine collection or postmortem tissue analysis. As groups, the patients given gentamicin and tobramycin did not differ in age, weight, creatine clearance, total dose given, duration of treatment, initial aminoglycoside through serum levels, number of dosage adjustments, concurrent use of furosemide, or concurrent cephalosporins. Previous aminoglycoside treatment (usually gentamicin) had occurred more frequently in the tobramycin treated patients (P less than 0.01), and more males than females received tobramycin (P less than 0.05). Pharmacokinetic assessments of renal damage were based on both changes in glomerular filtration rate (serum creatinine levels, creatinine clearance) and renal tubular damage (beta 2-microglobin, casts), but only patients with elevated aminoglycoside tissue levels leading to renal tubular damage and subsequent creatinine clearance decreases were considered to have experienced aminoglycoside nephrotoxicity. In the pharmacokinetic analysis of nephrotoxicity, 29 gentamicin courses (24%) and 12 tobramycin courses (10%) were complicated by nephrotoxicity (P less than 0.01). The 201 study patients were also evaluated independently for clinical nephrotoxicity (defined as a serum creatinine level increase of 0.5 mg/dl or more). Clinical nephrotoxicity occurred at rates of 37% in the gentamicin-treated group and 22% in the tobramycin-treated group (P less than 0.02). In these similar groups of critically ill patients, tobramycin was less nephrotic than gentamicin.
Plasma disappearance, urine excretion, and tissue distribution of ribavirin in rats and rhesus monkeys
Authors: Ferrara E A , Oishi J S , Wannemacher R W , Stephen E L
Published: June 2012

Ribavirin has been shown to have broad-spectrum antiviral. To study its tissue distribution and disappearance rate, a single dose of 10 mg/kg which contained 10 microCi of [14C]ribavirin was injected intravenously into rhesus monkeys and intramuscularly into monkeys and rats. Except for peak plasma concentrations and the initial phases of the plasma disappearance and urine excretion curves, no significant difference was observed between plasma, tissue, or urine values for intramuscularly or intravenously injected monkeys. Plasma disappearance curves were triphasic; plasma concentrations of ribavirin were similar for both monkeys and rats. Rats excreted ribavirin in the urine more rapidly and to a greater extent (82% excreted in 24 h) than did monkeys (60% excreted in 72 h). In the rat, only 3% of the injected [14C]ribavirin was detected in expired CO2. Therefore, for both species, urine was the major route for the elimination of labeled ribavirin and its metabolites from the body. In monkeys, the amount of parent drug in blood cells increased through 48 h and remained stable for 72 h, whereas in rats, ribavirin decreased at a rate similar to the plasma disappearance curve. Concentrations of ribavirin at 8 h were consistently higher in monkeys than in rats for all tissues except the brain. Thus, these differences in blood cellular components and organ content and in urine excretion suggested that there was greater tissue retention of ribavirin in monkeys than in rats.
Minimum inhibitory and bactericidal concentrations of 44 antimicrobial agents against three standard control strains in broth with and without human serum
Authors: Reimer L G , Stratton C W , Reller L B
Published: June 2012

Standard minimum inhibitory and bactericidal concentrations are not established for most antimicrobial agents against strains of bacteria commonly used for quality control in susceptibility testing. The effects of cation and human serum supplementation of broth on the values are also unknown. Therefore, we performed 10 minimum inhibitory and bactericidal concentration determinations for 44 antimicrobial agents against the standard control strains Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, and Pseudomonas aeruginosa ATCC 27853 in Mueller-Hinton broth and in Mueller-Hinton broth supplemented with calcium, magnesium, and 50% pooled human serum. Agreement of replicates was within one twofold dilution 97% of the time. Supplemented Mueller-Hinton broth gave higher minimum inhibitory concentrations for 24 antibiotics against S. aureus, for 17 drugs against E. coli, and for 12 drugs against P. aeruginosa, whereas it gave lower minimum inhibitory concentrations for 1 antibiotic against S. aureus, for 5 against E. coli, and for 5 against P. aeruginosa. Results for minimum bactericidal concentrations were similar. Added serum did not further affect the increased resistance of P. Aeruginosa to aminoglycosides encountered with cation supplementation of broth. These results provide expected values for the quality control strains when minimum inhibitory and bactericidal concentrations are determined in these two Mueller-Hinton media.
Cell Cultures Producing Human Interferon
Authors: Familletti Philip C. , Pestka Sidney
Published: June 2012

Most of 27 B-lymphoblast and 5 other cell lines derived from human leukocytes were found to produce human interferon either constitutively or after induction with Newcastle disease virus. Several produced relatively high levels of interferon after induction.
Competition of beta-lactam antibiotics for the penicillin-binding proteins of Neisseria gonorrhoeae
Authors: Dougherty T J , Koller A E , Tomasz A
Published: June 2012

The affinities of nine structurally different beta-lactam antibiotics for the three major gonococcal penicillin-binding proteins (PBPs) were determined by using a competition assay with tritium-labeled penicillin and live, growing bacteria. Each determination was carried out in parallel in isogenic pairs of penicillin-susceptible (minimal inhibitory concentration of penicillin, 0.0075 microgram/ml) and intrinsically penicillin-resistant (minimal inhibitory concentration of penicillin, 0.5 microgram/ml) cells. Evidence is presented indicating that (i) PBP 3 may be a dispensable function; (ii) acquisition of resistance is accompanied by change in the beta-lactam antibiotic affinities of PBP 2 but not of PBP 1; (iii) PBP 2 appears to be the most important physiological target in the penicillin-susceptible strain; in the penicillin-resistant strain, PBP 1 seems to assume this role. The relative affinities of various beta-lactam antibiotics for the individual PBPs showed substantial variation with the antibiotic structure.
Interferon production by a human lymphoblastoid cell line (DG-75) free of the Epstein-Barr genome
Authors: Lazar A , Reuveny S , Minai M , Traub A , Mizrahi A
Published: June 2012

A new lymphoblastoid cell line, DG-75, was investigated for its ability to produce interferon. DG-75 cells, previously shown to be free of Epstein-Barr virus genome and receptors, could be grown in submerged culture and could produce interferon in titers comparable to interferon produced by Namalva cells. The interferon produced was similar in size to the Namalva interferon as determined by gel filtration in Ultrogel AcA54. The DG-75 cells present a new source of large quantities of interferon which may be safer for human use than the Namalva interferon.
Influence of study design in assessing food effects on absorption of erythromycin base and erythromycin stearate
Authors: DiSanto A R , Chodos D J
Published: June 2012

We performed a series of six single-dose and multiple-dose studies to evaluate the effect of food on the absorption of erythromycin base and erythromycin stearate. When we used a single-dose design, we found that an unprotected erythromycin base preparation was absorbed extensively if a prolonged fast preceded administration of the drug. A shorter faster period (as occurs in clinical settings) dramatically reduced the absorption of unprotected base; however, film-coated tablets seemed to be as well protected as and were absorbed more rapidly than enteric-coated tablets when they were evaluated by single-dose testing procedures. In contrast, when a commercially available film-coated preparation of erythromycin base was evaluated in multidose fashion between meals (fasting), the drug was about 25% less well absorbed than commercially available enteric-coated base tablets. Finally, when commercially available film-coated erythromycin base and stearate formulations were administered with meals, both film-coated preparations were 43 to 59% less well absorbed than the enteric-coated base formulation. Furthermore, the enteric-coated base formulation performed equally well when administered either every 6 h between meals (fasting) or four times a day (immediately after meals and at bedtime). These studies document the need for multidose bioavailability techniques when the bioavailabilities of acid-labile drugs are evaluated.
Acyclovir treatment of experimental simian varicella infection of monkeys
Authors: Soike K F , Felsenfeld A D , Gerone P J
Published: June 2012

Replication of simian varicella virus (SVV) in Vero cell cultures was inhibited by acyclovir, 9-(2-hydroxyethoxymethyl)guanine (ACV), at a concentration of 10 micrograms/ml in culture medium. Intravenous administration of ACV at 10 mg/kg twice a day for 10 days or 15 mg/kg three times a day for 5 days to patas monkeys (Erythrocebus patas) beginning 48 h after SVV inoculation blocked the appearance of rash and other clinical symptoms but did not affect viremia. ACV treatment of African green monkeys (Cercopithecus aethiops) at 10 mg/kg twice a day by intravenous injection beginning 24 or 72 h after SVV inoculation and continuing for 10 days had no effect on clinical symptoms, including the development of rash, or on the appearance of viremia. The minimal therapeutic results could be due to the observation that doses of 10 or 15 mg/kg produced plasma levels of ACV which were lower than 5 micrograms/ml, the concentration that inhibited SVV multiplication in vitro, and decayed rapidly.
Minimal concentrations of aminoglycoside that can synergize with penicillin in enterococcal endocarditis
Authors: Carrizosa J , Levison M E
Published: June 2012

Minimal concentrations of aminoglycoside that could produce a synergistic effect with penicillin were investigated in broth cultures containing 10(8) enterococci per ml, in vitro in vegetations infected with ca. 10(8) enterococci per g, and in vivo in an experimental model of enterococcal endocarditis. Penicillin G plus gentamicin (1.5 or 0.75 microgram/ml) sterilized a broth culture of a streptomycin-resistant strain (E1) at 48 h. In contrast, penicillin G plus gentamicin (1.5 or 0.75 microgram/ml) sterilized only 2 of 15 in vitro vegetations at 5 days. Similarly, doses of gentamicin that resulted in peak serum levels of 1.5 microgram/ml failed after 10 days of therapy with penicillin G plus gentamicin to sterilize in vivo vegetations infected with E1, and doses of gentamicin that resulted in peak serum levels of about 8 micrograms/ml sterilized four of six vegetations. Similar results were obtained with a streptomycin-susceptible strain. These studies indicated that the rate of bactericidal activity in broth cultures is greater than the bacteriological response in infected vegetations and that aminoglycoside concentrations that appear efficacious on the basis of synergy studies in broth cultures may not be satisfactory clinically.
In vitro and in vivo studies of three antibiotic combinations against gram-negative bacteria and Staphylococcus aureus
Authors: Zinner S H , Klastersky J , Gaya H , Bernard C , Ryff J C
Published: June 2012

The activities of azlocillin, cefotaxime, and amikacin alone and in combination were evaluated in in vitro checkerboard studies, in infected neutropenic mice, and in human volunteers. The combination of cefotaxime plus amikacin was more synergistic in vitro than the others against the Enterobacteriaceae tested, and the combination of azlocillin plus amikacin was more synergistic against Pseudomonas aeruginosa and Staphylococcus aureus. Survival of neutropenic mice infected with Escherichia coli and Klebsiella pneumoniae, respectively, was greater with azlocillin plus amikacin (24 of 40 and 11 of 40) and with cefotaxime plus amikacin (21 of 40 and 17 of 40) than with azlocillin plus cefotaxime (22 of 40 and 3 of 40; P less than 0.05). Median serum bactericidal activity in volunteers receiving these antibiotics alone and in combination was greater than or equal to 1:8 with most agents and with all combinations tested against 10 strains each of E. coli, K. pneumoniae, P. aeruginosa, and S. aureus. These data suggest that clinical trials with combinations of azlocillin or cefotaxime plus amikacin deserve further study in febrile neutropenic patients.
Ticarcillin Bioassay
Authors: Bannatyne Robert M. , Cheung Rose
Published: June 2012

An accurate, plate diffusion bioassay for ticarcillin, utilizing the fast-replicating
Beneckea natriegens
and 4% salt agar, is described in this report. Zones of inhibition were well defined after 3 h, and the limit of sensitivity was around 5.0 μg/ml. The assay is simple to carry out, and duplicate assays can be performed on as little as 40 μl of serum.
Susceptibility of Mycobacterium marinum to tetracyclines and aminoglycosides
Authors: Wallace R J , Wiss K
Published: June 2012

Current agar dilution methods for susceptibility testing of Mycobacterium marinum versus the tetracyclines have failed to show in vitro susceptibility despite good in vivo results. We found that the tetracyclines were unstable in agar and resulted in a fine haze of growth for several concentrations before complete inhibition of growth was seen. In contrast, the aminoglycosides resulted in sharp minimal inhibitory concentration endpoints, which were generally independent of the length of incubation. The problems with the tetracyclines can be lessened by shortening the incubation time to 5 days and redefining the minimal inhibitory concentration as the lowest concentration resulting in no growth or a slight haze of growth. By this methodology, 19 clinical isolates of M. marinum were tested for susceptibility to the tetracyclines and aminoglycosides. Minocycline inhibited greater than 50% of isolates at 2.0 microgram/ml, whereas both minocycline and doxycycline inhibited greater than 90% of isolates at 4.0 microgram/ml. These studies support the usage of the tetracyclines in the treatment of clinical diseases due to M. marinum and suggest a susceptibility method which is more predictive of clinical results.
Antibacterial activity and beta-lactamase stability of ceftazidime, an aminothiazolyl cephalosporin potentially active against Pseudomonas aeruginosa
Authors: Neu H C , Labthavikul P
Published: June 2012

The in vitro activity and beta-lactamase stability of ceftazidime were evaluated against 700 gram-positive and gram-negative bacteria. Ceftazidime was less active than penicillins or older cephalosporins against Staphylococcus spp. and Streptococcus spp., and it did not inhibit Streptococcus faecalis, Listeria, or anaerobic species. Ceftazidime was as active as ceftizoxime and moxalactam and more active than cefoperazone against Escherichia coli. Klebsiella, and Proteus mirabilis with minimal inhibitory concentrations of less than 0.2 mg/liter. Ceftazidime also inhibited Enterobacter, Citrobacter, Salmonella, and Shigella at concentrations below 0.2 mg/liter. Most Morganella, Proteus rettgeri, Proteus vulgaris, and Proteus inconstans were inhibited at concentrations below 1 mg/liter, similar to the concentrations for moxalactam, ceftizoxime, and cefotaxime. Ceftazidime was the most active agent tested against Pseudomonas aeruginosa, with a mean minimal inhibitory concentration of 1.6 mg/liter. It inhibited carbenicillin-, piperacillin-, cefoperazone-, and cefsulodin-resistant Pseudomonas. Minimal inhibitory and minimal bactericidal concentrations were similar, with the exception of some Pseudomonas values at 10(7) colony-forming units. Use of different media did not alter minimal inhibitory concentration values. Ceftazidime was not hydrolyzed by staphylococcal beta-lactamase or plasmid beta-lactamase of the TEM-1, TEM-2, SHV-1, OXA-1, PSE-1, PSE-2 types or by inducible beta-lactamases of the cephalosporinase type. Ceftazidime provides an extremely active agent against aerobic and facultative gram-negative bacteria.
In vitro activity of moxalactam and mecillinam, singly and in combination, against multi-drug-resistant Enterobacteriaceae and Pseudomonas species
Authors: Fass R J
Published: June 2012

The in vitro interaction of moxalactam and mecillinam against multi-drug-resistant gram-negative enteric bacilli was studied by checkerboard microdilution susceptibility tests and by killing curve kinetics. Against Enterobacteriaceae, the combination was unpredictable; the frequencies of synergy, indifference, and antagonism were 11, 76, and 13%, respectively. Against Pseudomonas sp., the two drugs were consistently indifferent. Overall, the combination of moxalactam and mecillinam was no more active than moxalactam alone.
Mode of action of the biotin antimetabolites actithiazic acid and alpha-methyldethiobiotin
Authors: Eisenberg M A , Hsiung S C
Published: June 2012

Actithiazic acid and alpha-methyldethiobiotin inhibited the conversion of dethiobiotin to biotin resting-cell suspensions of Escherichia coli. The concentrations which effected 50% inhibition were 0.45 and 1.1 microM for actithiazic acid and alpha-methyldethiobiotin, respectively. Cells grown in low concentrations of the two biotin antimetabolites showed derepression of the biotin A operon, as evidenced by the enhanced levels of the enzymes 7,8-diaminopelargonic acid aminotransferase and dethiobiotin synthetase. Derepression was not due to any direct regulatory effect of the antibiotics but was the consequence of the inhibition of the biotin synthetase enzyme; this inhibition prevented the intracellular concentration of biotin from reaching the levels required for normal regulation of the biotin A operon.
Susceptibility testing of Campylobacter fetus subsp. jejuni, using broth microdilution panels
Authors: Buck G E , Kelly M T
Published: June 2012

Twenty-five isolates of Campylobacter fetus subsp. jejuni were tested by broth microdilution panels (Sensititre; GIBCO Diagnostics, Chagrin Falls, Ohio) and the minimal inhibitory concentrations (MICs) were compared with the corresponding MICs obtained by the standard agar dilution technique. Microdilution panels designed for testing gram-positive organisms were used so that erythromycin, the antibiotic of choice for this organism, could be included. The correlation with agar dilution was relatively poor when Mueller-Hinton broth was used; the MICs that were within one twofold dilution of the corresponding agar dilution MIC ranged from 15% with tetracycline to 75% with ampicillin. The overall agreement for all antibiotics tested was 48%. The correlation improved significantly, however, to an overall agreement of 87% when Wilkins-Chalgren broth was substituted in the broth microdilution procedure. Our results indicate that the broth microdilution test is an accurate method for testing this organism, provided than an appropriate medium is used.
In vitro activity of N-formimidoyl thienamycin and other beta-lactam antibiotics against methicillin-resistant Staphylococcus aureus
Authors: Thompson R L , Fisher K A , Wenzel R P
Published: June 2012

Of 43 isolates of methicillin-resistant Staphylococcus aureus, 90% were inhibited by 8 micrograms or less of N-formimidoyl thienamycin per ml by the agar-dilution technique. Cefamandole, cefotaxime, cefoperazone, moxalactam, and cefsulodin showed relatively poor activity. Vancomycin was the most active compound by weight, inhibiting 93% of strains at 1 microgram/ml.
Comparison of antimicrobial susceptibility patterns among coagulase-negative staphylococci
Authors: Price S B , Flournoy D J
Published: June 2012

Coagulase-negative staphylococci, identified as S. epidermidis, S. saprophyticus, S. haemolyticus, S. hominis, and S. warneri, were tested for susceptibility to a number of antimicrobial agents by disk agar diffusion and broth microdilution methods, S. warneri and S. saprophyticus were found to be the most susceptible, and S. haemolyticus and S. epidermidis were found to be the least susceptible. Differences in antimicrobial susceptibility patterns are discussed, along with their epidemiological and therapeutic implications.
Vancomycin pharmacokinetics in normal and morbidly obese subjects
Authors: Blouin R A , Bauer L A , Miller D D , Record K E , Griffen W O
Published: June 2012

In an uncontrolled study, vancomycin pharmacokinetics were determined in four normal (total body weight [TBW], 65.9 to 89.1 kg) and six morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese subjects were 4.8 h, 0.39 liter/kg, and 1.085 ml/min per kg versus 3.2 h, 0.26 liter/kg TBW, and 1.112 ml/min per kg TBW. The mean terminal half-life and volume of distribution values were significantly different between the two groups. Strong correlations were found between TBW and both volume of distribution (correlation coefficient, 0.943) and total body clearance (correlation coefficient, 0.981). There results implied that TBW should be used to calculate vancomycin doses for morbidly obese patients. This was supported by the finding that there was no significant difference in the daily dose (in milligrams per kilogram per day) required to produce an average steady-state concentration of 15 micrograms/ml in the two groups (23.4 +/- 1.5 mg/kg per day for normal weight subjects and 24.0 +/- 3.4 mg/kg per day TBW for the postsurgery morbidly obese subjects). Therefore, the morbidly obese required higher total doses (in milligrams per day) than did normal weight subjects to achieve the same mean steady-state concentrations. In addition, normal weight and morbidly obese subjects had similar volumes of the central compartment (7.7 and 6.4 liters, respectively). To avoid high transient peak concentrations which would occur when obese patients are given larger total doses (in milligrams per day), maintenance doses may be given at more frequent intervals. The shorter mean terminal half-lives observed in morbidly obese patients allows more frequent dosing without excessive accumulation.
Clinical and pharmacokinetic characteristics of aminoglycoside nephrotoxicity in 201 critically ill patients
Authors: Schentag J J , Cerra F B , Plaut M E
Published: June 2012

We studied 201 critically ill patients during 267 courses of gentamicin (139 courses) or tobramycin (128 courses) therapy. Clinical and pharmacokinetic data were obtained on 240 of 267 courses (120 courses each of gentamicin and tobramycin). Two judgments of nephrotoxicity and its cause were made independently in this study, using a clinical and a pharmacokinetic definition of nephrotoxicity. The two sets of criteria were generally in good agreement, as all but 10 of 41 patients who were judged nephrotoxic by pharmacokinetic criteria were independently judged nephrotoxic by the clinical definition. Groups of patients judged nontoxic did not differ from groups judged nephrotoxic in age, sex, weight, initial creatinine clearance, total dose given, duration of treatment, initial aminoglycoside trough serum levels, number of dosage adjustments, concurrent use of furosemide, or concurrent cephalosporins. Prior aminoglycosides (usually gentamicin) had been used more frequently in the nontoxic group (P less than 0.05). Two major conclusions of this study are at variance with those of previous investigators; (i) we found no clinical parameters of value in predicting nephrotoxicity in critically ill patients; and (ii) aminoglycoside serum concentrations, once in the therapeutic range, were of limited value in prevention of aminoglycoside nephrotoxicity in our patients.
Comparison of piperacillin and penicillin in the treatment of uncomplicated gonorrhea
Authors: Simpson M L , Khan M Y , Siddiqui Y , Gruninger R P , Wigren D I
Published: June 2012

A total of 120 men with uncomplicated infections caused by beta-lactamase-negative, highly penicillin-susceptible strains of Neisseria gonorrhoeae were included in this study. They were randomly assigned to regimens of either piperacillin (2.0 g) or procaine penicillin G (4.8 X 10(6) U) intramuscularly, both delivered concomitantly with an oral dose of 1.0 g probenecid. A total of 103 patients completed the study, providing data from 112 infected sites: for the penicillin regimen--urethra, 46; pharynx, 5; and rectum, 4; for the piperacillin regimen--urethra, 53; pharynx, 3; and rectum, 1. In the penicillin group, there were no failures at any of the infected sites. In the piperacillin group, all except one pharyngeal infection were cured. Also, in the piperacillin group, four men visit, whereas no cases of this type occurred in the penicillin group. No major side effects were noted in either group. Clinically, piperacillin was as effective as procaine penicillin G in the treatment of gonococcal urethritis in men. Pharyngeal infection may be refractory to piperacillin therapy.
Suppression of polymorphonuclear leukocyte chemotactic factor production in Propionibacterium acnes by subminimal inhibitory concentrations of tetracycline, ampicillin, minocycline, and erythromycin
Authors: Webster G F , Leyden J J , McGinley K J , McArthur W P
Published: June 2012

Propionibacterium acnes is the cause of inflammation in acne vulgaris and has been shown to produce potent neutrophil chemoattractants. Different strain of P. acnes that were sensitive or resistant to ampicillin, erythromycin, minocycline, and tetracycline were grown in the presence of subminimal inhibitory concentrations of the drugs, and their culture supernatants were assayed for neutrophil chemotactic activity. The presence of subminimal inhibitory concentrations of ampicillin failed to affect chemotactic factor production by any of the strains. Subminimal inhibitory concentrations of tetracycline, minocycline, and erythromycin all produced decreased neutrophil chemotactic activity in P. acnes culture supernatants. This inhibition of chemotactic activity was most pronounced in strains of P. acnes which were susceptible to the drugs. The addition of antibiotics at appropriate concentrations to control supernatants failed to affect neutrophil migration. The results indicate that subminimal inhibitory concentrations of antibiotics are capable of reducing the inflammatory capacity of P. acnes.
Comparative activities of 13 beta-lactam antibiotics
Authors: Muytjens H L , van der Ros-van de Repe J
Published: June 2012

An agar dilution method was used to measure the minimal inhibitory concentrations of 13 beta-lactam antibiotics against 868 recent human clinical isolates. Most members of the Enterobacteriaceae were susceptible to cefoperazone, ceftazidime, moxalactam, N-formimidoyl thienamycin, ceftriaxone, and ceftizoxime. Cephalothin was the most active antibiotic against Staphylococcus aureus. Most strains of Pseudomonas aeruginosa were inhibited by ceftazidime, N-formimidoyl thienamycin, and cefsulodin. N-Formimidoyl thienamycin was active against all of the species tested.
Single-dose pharmacokinetics of the monobactam azthreonam (SQ 26,776) in healthy subjects
Authors: Swabb E A , Sugerman A A , Platt T B , Pilkiewicz F G , Frantz M
Published: June 2012

Azthreonam (SQ 26,776) is a new, completely synthetic, monocyclic beta-lactam antimicrobial agent that is highly active in vitro against most gram-negative bacteria. The pharmacokinetics of single intravenous doses of 125 to 4,000 mg, studied in 36 healthy male subjects, were best described by an open, linear, two-compartment kinetic model. The mean peak serum levels at 5 min after completion of 3-min infusions of 500-, 1,000- and 2,000-mg doses were 58, 125, and 242 micrograms/ml, respectively. The mean terminal serum half-life for all doses was 1.66 h, and the apparent volume of distribution was 0.18 liter/kg. The mean serum clearance was 1.27 ml min-1 kg-1, and urinary excretion averaged 68% of the doses administered. The pharmacokinetics of single intramuscular doses of 250 to 1,000 mg, studied in 18 subjects, were best described by a linear, one-compartment model, with first-order absorption and elimination. The mean peak serum levels occurring at 1 h after doses of 250, 500, and 1,000 mg were 12, 22, and 46 micrograms/ml, respectively. Other kinetic parameters were similar to those for intravenous administration. Tolerance of azthreonam was good, with only a mild rash in one subject and with mild to moderate transient elevations in serum transaminases and lactate dehydrogenase in two subjects.
Pharmacokinetics and tolerance of ceftriaxone in humans after single-dose intramuscular administration in water and lidocaine diluents
Authors: Patel I H , Weinfeld R E , Konikoff J , Parsonnet M
Published: June 2012

The effects of 1% lidocaine as a diluent on the pharmacokinetics and tolerance of ceftriaxone administered intramuscularly were investigated in 12 adult volunteers. Each subject received two 0.5-g doses of ceftriaxone (one in water and the other in 1% lidocaine) at least 1 week apart in a randomized crossover fashion. Plasma and urine samples were collected serially and assayed for ceftriaxone content by high-performance liquid chromatography. The mean peak plasma concentration, time to attain the peak, area under the plasma curve from time zero to infinity, and elimination half-life were 45 micrograms/ml, 2.5 h, 578 micrograms . h/ml, and 7.1 h, respectively, after intramuscular administration of ceftriaxone in water diluent. The corresponding mean values in 1% lidocaine diluent were 42 micrograms/ml, 3 h, 577 micrograms . h/ml, and 7.0 h. The pharmacokinetic data suggested that 1% lidocaine does not alter either the elimination parameters or the bioavailability of intramuscularly administered ceftriaxone. The intensity and frequency of pain at the injection site were reduced considerably by the coadministered lidocaine.
Failure of Padac Test Strips to Detect Staphylococcal β-Lactamase
Authors: Anhalt John P. , Nelson Robert
Published: June 2012

Padac test strips failed to detect the production of β-lactamase by 10 strains of penicillin-resistant staphylococci.
In vitro susceptibility of streptococcus mutans 6715 to iodine and sodium fluoride, singly and in combination, at various pH values
Authors: Caufield P W , Wannemuehler Y M
Published: June 2012

The effect of pH on minimal bactericidal concentrations (MBCs) of sodium fluoride (NaF) and iodine (I2), singly and in combination, for Streptococcus mutans 6715 was investigated by using an in vitro checkerboard broth dilution assay. As pH was decreased, lower concentrations of NaF and I2 were required to exert a bactericidal effect. There was statistically significant linear correlation between pH and the MBCs of NaF (r = 0.95, P less than 0.001) and I2 (r ;.92, P less than 0.001). The MBCs of NaF were more affected by a change in pH than were the MBCs of I2; for every decrease of one pH unit in the range of pH 5 to 8, the MBC of NaF decreased fourfold, and the MBC of I2 decreased twofold. NaF and I2 in combination exhibited bactericidal effects on S. mutans which were additive at all pH values tested. These data indicated that the antibacterial properties of I2 and NaF, singly or in combination, can be enhanced by acidification.
Penicillin-resistant and penicillin-tolerant mutants of group A Streptococci
Authors: Gutmann L , Tomasz A
Published: June 2012

Penicillin-resistant and penicillin-tolerant mutants have been isolated from group A streptococci mutagenized by ethyl methane sulfonate. The resistant mutants had an elevated minimal growth inhibitory concentration for benzylpenicillin (minimal inhibitory concentration, 0.2 microgram/ml, as compared with the minimal inhibitory concentration of 0.006 microgram/ml in the penicillin-susceptible parent strain); they also had an abnormal cellular morphology and showed altered penicillin-binding proteins. Penicillin-tolerant mutants were killed more slowly than were the parental cells during treatment with penicillin; they had virtually unchanged minimal inhibitory concentration values for penicillin and normal cellular morphology and penicillin-binding proteins.
Yersinia enterocolitica
: Comparative In Vitro Activities of Seven New β-Lactam Antibiotics
Authors: Scribner R. K. , Marks M. I. , Weber A. , Pai C. H.
Published: June 2012

Minimum inhibitory concentrations of seven new β-lactam derivatives were determined against 35 isolates of
Yersinia enterocolitica
. Ceftizoxime and ceftriaxone were the most active of the antimicrobial agents tested.
Transfer of IncN plasmids to Pseudomonas aeruginosa
Authors: Tardif G , Grant R B
Published: June 2012

Three of four N plasmids tested were found to be conjugatively transferable from Escherichia coli to Pseudomonas aeruginosa. The plasmids in the Pseudomonas transconjugants differed from the plasmids in the donor E. coli with respect to molecular weight, transfer ability, phenotype conferred, and stability. In some cases, the antibiotic and UV resistance genes appeared to integrate into the P. aeruginosa chromosome.
Pharmacokinetics of ketoconazole in patients with neoplastic diseases
Authors: Maksymiuk A W , Levine H B , Bodey G P
Published: June 2012

Twenty-seven patients with advanced malignancies were given 200 mg of ketoconazole orally every 6 or 12 h. Blood samples were collected during these intervals and after the last dose to determine plasma concentrations and half-lives. The mean plasma concentrations measured after the initial dose were 1.7 +/- 1.1 microgram/ml at 2 h, 0.9 +/- 0.2 microgram/ml at 6 h, and 0.7 +/- 0.4 microgram/ml at 8 h. Plasma concentrations rose significantly in patients on the every-6-h schedule. Concentrations were more variable in patients on the every-12-h schedule, and changes in mean plasma concentrations after 7 and 14 days were not significant. Half-lives ranged from 1.3 to 11.6 h in individual patients. The mean half-life for all patients studied was 3.7 +/- 0.6 h on day 1. The calculated area under the curve was 12.0 +/- 4.7 micrograms-h/ml on day 1; it increased after 7 and 14 days of administration (every-6-h schedule), suggesting plasma binding or wide drug distribution or both. Saturation of storage compartments is also suggested. Less than 1% of the administered dose was recoverable as active drug from the urine over 6 h.
In vitro antibacterial activity of E-0702, a new semisynthetic cephalosporin
Authors: Katsu K , Kitoh K , Inoue M , Mitsuhashi S
Published: June 2012

E-0702 is an antipseudomonal cephalosporin derivative which has a broad spectrum of antibacterial activity against clinical isolates of gram-positive and gram-negative bacteria. Its in vitro antibacterial activities were less than those of cefoperazone and cefotaxime against Staphylococcus aureus and Staphylococcus epidermidis, but were significantly high against gram-negative bacteria including the Pseudomonas group. It was most characteristic that E-0702 showed high antibacterial activity against Pseudomonas aeruginosa. E-0702 was relatively stable to inactivation by plasmid-mediated penicillinases and cephalosporinases produced by gram-negative bacteria.
Carbenicillin resistance of Pseudomonas aeruginosa
Authors: Rodríguez-Tebar A , Rojo F , Dámaso D , Vázquez D
Published: June 2012

Four strains of Pseudomonas aeruginosa obtained from clinical isolates which are carbenicillin resistant were studied to find the cause(s) of resistance to this beta-lactam antibiotic. The electrophoresis patterns of the four strains (PH20610, PH20815, PH4011, and PH4301) were found to be different from those of a wild-type strain, P. aeruginosa NCTC 10662, and appeared to lack penicillin-binding protein 2. Affinity of other penicillin-binding proteins from strains PH20610 and PH20815 for carbenicillin seemed to be normal or slightly diminished. Electrophoretic patterns of penicillin-binding proteins from strains PH4011 and PH4301 had more profound differences, since the affinities of their penicillin-binding proteins 1a, 1b, and 4 for carbenicillin were decreased by nearly two orders of magnitude relative to the preparations from the wild-type strain. Kinetic studies on binding of carbenicillin to penicillin-binding proteins both in isolated membrane preparations and in intact cells revealed that carbenicillin penetration into resistant cells was a much slower process than in susceptible cells, suggesting that the outer envelope structures serve as an efficient barrier against carbenicillin entry into our P. aeruginosa strains from clinical isolates.
Pharmacokinetics of vancomycin: observations in 28 patients and dosage recommendations
Authors: Rotschafer J C , Crossley K , Zaske D E , Mead K , Sawchuk R J , Solem L D
Published: June 2012

Studies of the pharmacokinetics of vancomycin were conducted in a group of 28 patients with serious staphylococcal infection. Serum specimens were collected before and on 11 occasions after vancomycin administration. Serum concentration time data were fitted to a biexponential equation, using nonlinear regression analysis. A prolonged distribution phase with a half-life of 0.5 +/- 0.3 h (standard deviation) and a central component volume of 9.0 +/- 4.0 liters were demonstrated. Wide interpatient variation was observed in the terminal half-life which ranged from 3 to 13 h (mean, 6 h) and in the distribution volume which ranged from 14 to 111 liters (mean, 39 liters). A correlation of 0.45 (Pearson product moment correlation coefficient) was found between vancomycin clearance and creatinine clearance. Multiple regression analyses demonstrated that 50% of the variance (R2) in the terminal half-life and vancomycin clearance could be explained on the basis of renal function, volume of distribution, age, weight, and sex. These observations suggest that adults with normal renal function should receive an initial dosage of 6.5 to 8 mg of vancomycin per kg intravenously over 1 h every 6 to 12 h. After 24 h, and through the period of therapy, trough and peak serum vancomycin concentrations should be monitored, and the dose and dosage interval should be changed to produce the desired peak (30 to 40 micrograms/ml) and trough (5 to 10 micrograms/ml) levels.
In vitro susceptibilities of Aeromonas hydrophila against new antibiotics
Authors: Fainstein V , Weaver S , Bodey G P
Published: June 2012

The antibiotic susceptibilities of 16 clinical isolates of Aeromonas hydrophila obtained from cancer patients with septicemia were studied. Of the new beta-lactam antibiotics tested, azthreonam and moxalactam were the most active, followed by cefoperazone, cefotaxime, and ceftizoxime. Excellent activity was demonstrated by chloroamphenicol, tetracycline, aminoglycosides, and trimethoprim-sulfamethoxazole. Semisynthetic penicillins had no appreciable activity against this organism.
Mutation frequency of Haemophilus influenzae to rifampin resistance
Authors: Mendelman P M , Roberts M C , Smith A L
Published: June 2012

Twenty-two susceptible strains of Haemophilus influenzae were examined for mutation to rifampin resistance (minimal inhibitory concentration, greater than or equal to 10 micrograms/ml). All strains had detectable apparent mutation frequencies with a median minimal inhibitory concentration 2,000-fold greater than that of their wild-type parents. Of the type b strain mutants, 80% (8 of 10) expressed high-level resistance (minimal inhibitory concentration, 750 micrograms/ml) that was 75-fold greater than readily achievable serum concentrations.
Thiolutin-resistant mutants of Salmonella typhimurium
Authors: Joshi A , Verma M , Chakravorty M
Published: June 2012

Spontaneous mutants of Salmonella typhimurium isolated in our laboratory from thiolutin-containing tryptone agar plates are partially resistant to thiolutin in enriched media. In minimal media, they are not resistant. The mutants are not temperature sensitive but fail to support the development of phage P22 at higher temperatures (40 degrees C). Thiolutin did not interfere with RNA polymerase or nucleotide kinase in in vitro experiments. However, thiolutin did inhibit the rate of incorporation of exogenous uridine into the cellular pool and consequently the acid-precipitable material. It appears that one site of action of thiolutin is at the membrane level.
In vitro and in vivo activity of DL-8280, a new oxazine derivative
Authors: Sato K , Matsuura Y , Inoue M , Une T , Osada Y , Ogawa H , Mitsuhashi S
Published: June 2012

DL-8280, 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H- pyrido-(1,2,3-de)1,4-benzoxazine-6-carboxylic acid, is a new nalidixic acid analog with a broad spectrum of antibacterial activity against gram-negative and gram-positive bacteria, including obligate anaerobes. The activity of DL-8280 against Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae, Neisseria gonorrhoeae, and Clostridium perfringens was roughly comparable to that of norfloxacin and far exceeded that of pipemidic acid and nalidixic acid. DL-8280 had greater activity against Staphylococcus spp., Streptococcus spp., Pseudomonas maltophilia, Acinetobacter spp., and Bacteroides fragilis than did norfloxacin, pipemidic acid, and nalidixic acid. Nalidixic acid-resistant Enterobacteriaceae, ampicillin-resistant gonococci, and clindamycin-resistant obligate anaerobes were also susceptible to DL-8280. The activity of DL-8280 was affected very little by inoculum size, and its action was bactericidal at two times the minimal inhibitory concentrations at most. Administered orally to mice experimentally infected with Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Serratia marcescens, or P. aeruginosa, DL-8280 was 2 to 7 times more effective than norfloxacin and 7 to more than 50 times more active than pipemidic acid.
Outer membrane permeation of beta-lactam antibiotics in Escherichia coli, Proteus mirabilis, and Enterobacter cloacae
Authors: Sawai T , Hiruma R , Kawana N , Kaneko M , Taniyasu F , Inami A
Published: June 2012

Mutant strains lacking outer membrane protein(s) were isolated from Escherichia coli, Proteus mirabilis, and Enterobacter cloacae. The outer membrane protein(s) of P. mirabilis and E. cloacae corresponding to E. coli porin were identified on the basis of their function, namely, their ability to allow the permeation of glucose as demonstrated by [14C]glucose uptake by intact cells. P. mirabilis has only one outer membrane pore protein (molecular weight, 40,000), but E. cloacae has at least two such proteins (molecular weights, 37,000 and 39,000 to 40,000). When the bacteria lost these proteins or porin, the outer membrane permeation of cefazolin was found to be greatly reduced in these three species. Such a change in the outer membrane permeation closely correlated with a significant decrease in the bacterial susceptibility to cephalosporins, including cefoxitin. These results suggested that the main pathway for cephalosporin permeation is the pore made up of these proteins. The 39,000- to 40,000-molecular-weight protein in E. cloacae was also assumed to play an important role in the outer membrane permeation of tetracycline and chloramphenicol. On the other hand, the permeation route of penicillins was obscure. The susceptibility to penicillins, except in some cases, was little influenced by the absence of the proteins. Ampicillin was found to pass through the outer membrane via the same route as the cephalosporins, but the possibility that ampicillin and other penicillins possess another unknown route for outer membrane permeation could not be ruled out.
Influence of subinhibitory concentrations of penicillin, cephalothin, and clindamycin on Staphylococcus aureus growth in human phagocytic cells
Authors: Elliott G R , Peterson P K , Verbrugh H A , Freiberg M R , Hoidal J R , Quie P G
Published: June 2012

After an initial 2-h incubation with phagocytic cells, the growth of surviving intracellular Staphylococcus aureus was examined in the presence of subinhibitory concentrations of penicillin, cephalothin, and clindamycin. One-tenth of the minimal inhibitory concentrations of these antibiotics markedly reduced bacterial growth in normal polymorphonuclear leukocytes. In contrast, when human alveolar macrophages were studied, no inhibition of growth was seen. Subinhibitory concentrations of these antibiotics and polymorphonuclear leukocytes acted synergistically to reduce intracellular survival of S. aureus. This synergy did not appear to be dependent upon the microbicidal potential of the leukocyte respiratory burst, since no differences were found when polymorphonuclear leukocytes obtained from patients with chronic granulomatous disease were compared with those from normal donors.