bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro and in vivo antibacterial properties of FK 027, a new orally active cephem antibiotic
Authors: Kamimura T , Kojo H , Matsumoto Y , Mine Y , Goto S , Kuwahara S
Published: June 2012

FK 027 was more active than cefaclor, cephalexin, and amoxicillin against stock strains of a wide variety of gram-negative bacteria, including such opportunistic pathogens as Citrobacter and Enterobacter species and Serratia marcescens. FK 027 was significantly more active than the three reference drugs against clinical isolates of Escherichia coli, Klebsiella pneumoniae, indole-positive and -negative Proteus species, Providencia species, Haemophilus influenzae, and Neisseria gonorrhoeae. It was less active than cefaclor, cephalexin, and amoxicillin against staphylococci, but it was similar to cefaclor in its activity against streptococci. With few exceptions, FK 027 was active against strains of E. coli, K. pneumoniae, and Proteus mirabilis that were resistant to the reference agents. The bactericidal activity of FK 027 against various gram-negative bacteria, including Proteus species, Citrobacter freundii, Enterobacter aerogenes, and S. marcescens, was greater than that of cefaclor, cephalexin, and amoxicillin. The therapeutic activities of FK 027 in mice infected with gram-negative bacilli were far superior to the activities of cefaclor, cephalexin, and amoxicillin, but they were inferior to the activities of these reference drugs against infection with Staphylococcus aureus.
Gentamicin, netilmicin, dibekacin, and amikacin nephrotoxicity and its relationship to tubular reabsorption in rabbits
Authors: Brion N , Barge J , Godefroy I , Dromer F , Dubois C , Contrepois A , Carbon C
Published: June 2012

The role of the tubular reabsorption of aminoglycosides in nephrotoxicity was considered. The tubular reabsorption rate, fractional reabsorption, and net balance, expressed as the excreted to infused aminoglycoside ratio, were concomitantly studied in male rabbits by continuous infusion of gentamicin, netilmicin, dibekacin, and amikacin. Aminoglycoside nephrotoxicity was evaluated by creatinine levels in serum and pathological renal damage after 14 days of a low- or high-dose regimen, comprising either eight, hourly intramuscular injections of gentamicin, netilmicin, or dibekacin (4 mg/kg) or amikacin (16 mg/kg); twelve, hourly intramuscular injections of gentamicin, netilmicin, or dibekacin (15 mg/kg) or amikacin (60 mg/kg); or injections of saline for the control group. Aminoglycosides exhibited three degrees of tubular reabsorption: gentamicin had the highest, netilmicin had the lowest, and dibekacin and amikacin had intermediate degrees of reabsorption. Nephrotoxicity associated with alteration in renal histology was observed with gentamicin and, to a lesser extent, with dibekacin in the high-dose regiment. No nephrotoxicity was noted with netilmicin or amikacin compared with the control group. Concentrations of the aminoglycosides in renal cortex and serum were not predictive of renal toxicity. Except for amikacin, which appeared to exhibit the lowest intrinsic renal toxicity, nephrotoxicity was correlated with the tubular reabsorption of each aminoglycoside. It was concluded that aminoglycoside renal toxicity can be determined by two major factors: importance of transport into tubular cells and intrinsic intracellular toxicity.
In vitro antimicrobial activity of aztreonam alone and in combination against bacterial isolates from pediatric patients
Authors: Stutman H R , Welch D F , Scribner R K , Marks M I
Published: June 2012

We examined 134 pediatric clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa, and gram-positive cocci for susceptibility to aztreonam alone and in combination with seven other antibiotics. All 98 gram-negative isolates were susceptible to aztreonam with similar inhibitory and bactericidal activity. Combinations of aztreonam with cefoxitin, ampicillin, or clindamycin were generally indifferent or additive. Synergism was occasionally seen against enteric organisms with aztreonam plus cefoxitin or clindamycin. Combinations of tobramycin and aztreonam were synergistic (62%) against P. aeruginosa; aztreonam plus piperacillin or ticarcillin was additive. Aztreonam did not affect the activity of nafcillin against Staphylococcus aureus, or of ampicillin against species of Streptococcus group B or D. Antagonism was seen only with aztreonam plus cefoxitin against Enterobacter species, but not at clinically significant concentrations. Several combinations of antibiotics with aztreonam should be appropriate for initial therapy of infections in children without major risks of antibacterial antagonism.
Relation between aminoglycoside 2"-O-nucleotidyltransferase activity and aminoglycoside resistance
Authors: Bongaerts G P , Molendijk L
Published: June 2012

The relationship between plasmid-coded aminoglycoside 2"-O-nucleotidyltransferase [ANT(2")] activity and the minimum inhibitory concentration for aminoglycosides was studied. ANT(2") was very unstable, and therefore, procedures for handling this enzyme were optimized. Escherichia coli L58058.1 producing ANT(2") was resistant to gentamicin, sisomicin, kanamycin, tobramycin, and dibekacin but susceptible to netilmicin, amikacin, and neomycin. However, only amikacin and neomycin were not modified by ANT(2"). A correlation between the substrate profile of the enzyme tested at 0.15 mM and the minimum inhibitory concentrations of the aminoglycosides could not be demonstrated. The substrate concentration-dependent enzyme activity curves proved to be a better alternative than a substrate profile based on tests at one concentration. At concentrations of greater than 10(-2) mM, ANT(2") demonstrated substrate inhibition that explains the discrepancy between ANT(2") activity and the minimum inhibitory concentrations. A close correlation was found between the physiological efficiency (Vmax/Km ratio) of ANT(2") and the minimum inhibitory concentrations for the enzyme-producing strain.
Purification and properties of a cell-bound bacteriocin from a Bacteroides fragilis strain
Authors: Southern J A , Katz W , Woods D R
Published: June 2012

A cell-bound bacteriocin was extracted from a Bacteroides fragilis BF-11 strain by treating the cells with a low-molarity buffer (0.01 M Tris-hydrochloride, pH 8.0). Sucrose osmotic shock experiments and ultrasonic lysis of whole cells indicated that the majority of the bacteriocin was located at the cell surface. Culture supernatants contained no significant bacteriocin activity. The bacteriocin was purified by DEAE-cellulose and Sephacryl S200 chromatography and had an apparent molecular weight of approximately 7,000. It was relatively heat stable and was inactivated by proteases. There was a delay of approximately 3.5 h before DNA, RNA, and protein synthesis were inhibited by the bacteriocin. Inhibition of macromolecular synthesis coincided with lysis of the susceptible indicator strain.
Treatment of bacterial meningitis with ceftizoxime
Authors: Overturf G D , Cable D C , Forthal D N , Shikuma C
Published: June 2012

Ceftizoxime was evaluated in the treatment of 18 patients (6 adults and 12 children) with bacterial meningitis. In seven patients Haemophilus influenzae was the causative agent, in three Neisseria meningitidis, in five Streptococcus pneumoniae, and in one each alpha-streptococcus and Escherichia coli; one case was culture negative. Ceftizoxime was administered intravenously in doses of 200 mg/kg per day. Clinical response was appropriate in all patients with a mean time of defervescence of 3.7 days, and sterile cerebrospinal fluid was obtained from all patients at 24 to 36 h after initiation of therapy. The mean concentration of ceftizoxime in 46 cerebrospinal fluid samples obtained during therapy was 8.53 micrograms/ml (range, less than 0.5 to 29.0 micrograms/ml). Ceftizoxime concentrations in cerebrospinal fluid samples were ten- to several hundredfold the bactericidal concentrations of the pathogens isolated from the cerebrospinal fluid. Ceftizoxime penetrates the meninges well during acute infection and appears to be an excellent candidate antibiotic in the treatment of bacterial meningitis.
Ketoconazole in the prevention of experimental candidal vaginitis
Authors: Sobel J D , Muller G
Published: June 2012

The prophylactic and therapeutic activities of ketoconazole were evaluated in rats inoculated intravaginally with Candida albicans. Daily doses of 2.5 mg/kg initiated 48 h before challenge and continued for 48 h thereafter protected 80% of the rats against infection. A similar result in rats with established infection was attained with daily doses of 5.0 mg/kg.
In vitro activity of aztreonam in combination with newer beta-lactams and amikacin against multiply resistant gram-negative bacilli
Authors: Buesing M A , Jorgensen J H
Published: June 2012

The in vitro synergistic activity of aztreonam in combination with piperacillin, moxalactam, cefotaxime, cefoperazone, and amikacin was examined against multiply resistant isolates of the family Enterobacteriaceae and Pseudomonas aeruginosa. Aztreonam in combination with amikacin demonstrated synergy against 71% of the isolates, whereas combinations of aztreonam plus a second beta-lactam demonstrated synergy against 42% of the isolates.
Broad host range of streptococcal macrolide resistance plasmids
Authors: Buu-Hoï A , Bieth G , Horaud T
Published: June 2012

Four macrolide-lincosamide-streptogramin B resistance plasmids transferred into 13 recipients belonging to Streptococcus, Staphylococcus, and Listeria genera. The plasmids were stably maintained in all new hosts except Streptococcus sanguis, Streptococcus pneumoniae, Staphylococcus aureus, and Listeria innocua and were identical to those found in the corresponding donor strains.
Biological action of inosine analogs in Leishmania and Trypanosoma spp
Authors: Marr J J , Berens R L , Cohn N K , Nelson D J , Klein R S
Published: June 2012

Previous investigations have suggested that inosine analogs would be good models for the development of chemotherapeutic agents active against pathogenic hemoflagellates. We have systematically modified the five-membered heterocyclic ring of six inosine analogs and tested them for their antiprotozoal activities and toxicity to a mammalian cell line. All six analogs were very active against the three protozoan pathogens Leishmania donovani, Trypanosoma cruzi, and Trypanosoma gambiense. Two of the six, 9-deazainosine and allopurinol ribonucleoside, had very little toxicity for mouse L cells and offer promise as potential chemotherapeutic agents.
Pharmacokinetics of metronidazole in patients undergoing continuous ambulatory peritoneal dialysis
Authors: Guay D R , Meatherall R C , Baxter H , Jacyk W R , Penner B
Published: June 2012

The pharmacokinetics of metronidazole, its biologically active alcohol metabolite, and its inactive acid metabolite were studied in five noninfected patients undergoing continuous ambulatory peritoneal dialysis and five patients undergoing hemodialysis. The latter were studied on off-dialysis days as a control group. Peritoneal dialysis caused insignificant changes in the apparent volume of distribution, elimination half-life, and total body clearance of metronidazole. Peritoneal dialysis clearance (4.49 +/- 0.88 ml/kg per h [mean +/- standard deviation]) accounted for only 8.9% of total body clearance (50.17 +/- 18.64 ml/kg per h). Analysis of the 24-h area under the serum concentration versus time curves and peritoneal dialysis clearance data for the two metabolites suggested a similar insignificant effect of peritoneal dialysis on their elimination. Metronidazole dialysate concentrations in the first 6-h exchange ranged from 7.6 to 11.7 micrograms/ml. This would suggest that cumulative penetration of metronidazole from the systemic circulation into the peritoneal cavity with dosing every 8 h should lead to adequate concentrations for the treatment of anaerobic peritonitis. For the treatment of systemic anaerobic infections, it would appear at present that metronidazole dosage adjustments are not necessary in patients undergoing continuous ambulatory peritoneal dialysis. The potential for metabolite accumulation was noted in this study. If further studies confirm that excessive serum metabolite concentrations are toxic, dosage reduction in this group of patients may be warranted.
Bactericidal activities of chloramphenicol and eleven other antibiotics against Salmonella spp
Authors: Preblud S R , Gill C J , Campos J M
Published: June 2012

The bactericidal activity of chloramphenicol against 27 strains of Salmonella typhi and 33 strains of S. enteritidis was compared with those of 11 other antibiotics. The geometric mean bactericidal concentrations of chloramphenicol against susceptible strains (36.10 and 43.13 micrograms/ml for S. typhi and S. enteritidis, respectively) far exceeded those of the other 11 antibiotics, with cephalothin having the next highest values (2.67 and 8.66 micrograms/ml) and moxalactam (0.09 and 0.28 micrograms/ml), cefotaxime (0.08 and 0.28 micrograms/ml), ceftriaxone (0.07 and 0.16 micrograms/ml), norfloxacin (0.06 and 0.10 micrograms/ml), and aztreonam (0.05 and 0.20 micrograms/ml) having the lowest values. The results for imipenem (0.24 and 0.81 micrograms/ml) and ceftazidime (0.22 and 0.75 micrograms/ml) were lower than those noted for trimethoprim-sulfamethoxazole (1.20 and 5.56 micrograms/ml), cefamandole (0.62 and 3.29 micrograms/ml), and ampicillin (0.55 and 2.78 micrograms/ml). The MBC of chloramphenicol for some isolates decreased with increased incubation times such that the proportion of susceptible isolates killed by chloramphenicol at concentrations within achievable levels in blood increased from 10% after 24 h to 26% after 48 h of incubation. Although the MBC of the other 11 antibiotics for some isolates were also lowered by prolonged incubation, all 24-h values were within achievable levels in blood. The data indicate that chloramphenicol is not uniformly bacteriostatic against S. typhi and S. enteritidis. The in vivo significance of demonstrating delayed killing by chloramphenicol is, however, uncertain.
In vitro activity of ciprofloxacin, a new carboxyquinoline antimicrobial agent
Authors: Eliopoulos G M , Gardella A , Moellering R C
Published: June 2012

The in vitro activity of ciprofloxacin (Bay o 9867), a new carboxyquinoline antimicrobial agent, was compared with those of norfloxacin, nalidixic acid, and several other oral and parenteral antimicrobial agents. Ciprofloxacin was substantially more active than nalidixic acid or cinoxacin against all gram-negative bacteria tested. Virtually all strains of Enterobacteriaceae were inhibited by the new drug at concentrations of less than or equal to 0.125 micrograms/ml. Ciprofloxacin was more active than norfloxacin against Klebsiella sp., Enterobacter sp., and Serratia marcescens, and it was the most active agent against Pseudomonas aeruginosa (MIC90, 0.5 micrograms/ml). The new drug also demonstrated significant activity against gram-positive cocci, inhibiting all strains of staphylococci at concentrations of less than or equal to 1.0 microgram/ml. Ciprofloxacin was bactericidal at concentrations near the MIC against most isolates tested. Although stepwise increases in resistance were seen with Escherichia coli and P. aeruginosa during serial passage on plates containing incremental concentrations of the drug, significant resistance did not emerge during incubation of strains in broth containing concentrations of ciprofloxacin above the MBC.
Effect of inoculum, pH, and medium on the activity of ciprofloxacin against anaerobic bacteria
Authors: Borobio M V , Perea E J
Published: June 2012

The in vitro activity of ciprofloxacin against 30 Bacteroides fragilis group, 30 Clostridium, and 30 Peptococcaceae strains was determined by the agar dilution method in two different culture media at three pH and in three inoculum densities. In Wilkins-Chalgren agar the MICs for 90% of the strains were 0.12 micrograms/ml for B. fragilis, 0.5 micrograms/ml for Clostridium spp., and 2 micrograms/ml for Peptococcaceae. The pH and medium composition affected the MICs of ciprofloxacin.
Influence of tetracyclines on human polymorphonuclear leukocyte function
Authors: Glette J , Sandberg S , Hopen G , Solberg C O
Published: June 2012

Low concentrations of oxytetracycline, doxycycline, or minocycline (less than 10 micrograms/ml) did not influence in vitro polymorphonuclear leukocyte random migration, chemiluminescence, or glucose oxidation. At high concentrations of doxycycline or minocycline (greater than 10 micrograms/ml), chemiluminescence and glucose oxidation were impaired. High concentrations of doxycycline also reduced random migration. Oxytetracycline did not influence these functions in concentrations up to 100 micrograms/ml. The inhibiting effect of doxycycline and minocycline was abolished when 4 mM Mg2+ was added to the reaction mixture, and 4 mM Ca2+ partly restored minocycline-inhibited polymorphonuclear leukocyte functions. This indicates that the major effect of tetracyclines on in vitro polymorphonuclear leukocyte functions is mediated by their divalent cation chelating effect and that the results of in vitro experiments are highly dependent on the concentration of divalent cations in the reaction mixtures. The difference between the tetracyclines may be due to differences in lipid solubility, with solubility being highest for minocycline and lowest for oxytetracycline, or to different divalent cation chelating ability.
Susceptibilities of bacterial and fungal urinary tract isolates to desferrioxamine
Authors: Lowy F D , Pollack S , Fadl-Allah N , Steigbigel N H
Published: June 2012

Desferrioxamine, a safe and effective iron chelator, was evaluated for its antibacterial and antifungal activity. The susceptibilities of 124 urinary tract isolates and 28 clinical isolates of Neisseria gonorrhoeae to desferrioxamine concentrations that are readily achievable in urine were determined. Of all isolates, 27% were inhibited by a concentration of less than or equal to 12.5 mM. Proteus mirabilis and N. gonorrhoeae isolates were particularly susceptible to the chelator. Desferrioxamine appears to have limited potential as an antibacterial agent.
In vitro susceptibilities of 393 recent clinical isolates to WIN 49375, cefotaxime, tobramycin, and piperacillin
Authors: Pohlod D J , Saravolatz L D
Published: June 2012

The in vitro susceptibilities of 393 recent clinical isolates to WIN 49375, a new quinolone derivative, were determined and concurrently tested with cefotaxime, tobramycin, and piperacillin. In general, members of the family Enterobacteriaceae were not as susceptible to tobramycin and piperacillin as they were to WIN 49375. Methicillin-resistant and -susceptible Staphylococcus aureus were equally susceptible to WIN 49375.
Production of hypoprothrombinemia by moxalactam and 1-methyl-5-thiotetrazole in rats
Authors: Lipsky J J , Lewis J C , Novick W J
Published: June 2012

To determine whether the hypoprothrombinemia associated with antibiotics containing a 1-methyl-5-thiotetrazole (MTT) group is a result of the presence of the MTT group, rats were maintained on a vitamin K-deficient diet for 10 days and then received either intravenous moxalactam or cefotaxime or oral MTT for two additional days. MTT and moxalactam, which contains the MTT group, prolonged prothrombin time. Cefotaxime, which lacks the MTT group, had no effect.
In vitro activity of U-63196E, a new cephalosporin, against clinical bacterial isolates
Authors: Eliopoulos G M , Gardella A , DeGirolami P , Moellering R C
Published: June 2012

The in vitro activity of U-63196E, a new cephalosporin, was compared with those of other extended-spectrum cephalosporins and penicillins against clinical bacterial isolates. Against Pseudomonas aeruginosa, the activity of U-63196E was comparable to those of cefoperazone and piperacillin, each of which inhibited 90% of strains at concentrations of less than or equal to 16 micrograms/ml. The new drug also demonstrated activity against a variety of other bacterial species, but it was generally less active than cefotaxime, moxalactam, and cefoperazone against members of the family Enterobacteriaceae and staphylococci. The presence of any 1 of 10 plasmid-mediated beta-lactamases in a series of otherwise isogenic laboratory strains of P. aeruginosa resulted in a significant reduction in the activity of U-63196E in comparison with its activity against the parent strain, which lacks these enzymes. Combinations of U-63196E with tobramycin demonstrated bacteriostatic synergism against 11 of 20 clinical isolates of P. aeruginosa.
Comparative efficacies of mezlocillin and ampicillin alone or in combination with gentamicin in the treatment of Streptococcus faecalis endocarditis in rabbits
Authors: Fass R J , Wright C A
Published: June 2012

The in vitro and in vivo activities of mezlocillin and ampicillin, alone and in combination with gentamicin, against Streptococcus faecalis were compared. In vitro, relative bactericidal and activities for 10 strains of S. faecalis were as follows: mezlocillin plus gentamicin greater than ampicillin plus gentamicin (P is not significant) greater than mezlocillin (P less than 0.01) greater than ampicillin (P less than 0.01) greater than gentamicin (P less than 0.01) greater than control (P less than 0.01). One of the strains was used to induce endocarditis in rabbits. Infected rabbits were treated by random selection with ampicillin, mezlocillin, ampicillin plus gentamicin, mezlocillin plus gentamicin, or saline (control) for 7 days. Among antibiotic-treated rabbits, survival rates were the same, but ampicillin was less effective than the other regimens in sterilizing both blood cultures (P less than 0.001 on day 4) and cardiac vegetations (P less than 0.05 on day 7). Differences in quantitative vegetation cultures among rabbits treated with mezlocillin, mezlocillin plus gentamicin, or ampicillin plus gentamicin and sacrificed on day 7 were not significantly different. Peak inhibitory and bactericidal antibacterial activity titers in serum determined during treatment were higher with mezlocillin (with or without gentamicin) than with ampicillin (with or without gentamicin) (P less than 0.01). Mezlocillin may be more effective than ampicillin in the treatment of S. faecalis infections in humans.
Effect of rifampin and bacitracin on nasal carriers of Staphylococcus aureus
Authors: McAnally T P , Lewis M R , Brown D R
Published: June 2012

Anterior nares cultures from 664 hospital personnel identified 165 (24.8%) as carriers of Staphylococcus aureus. Persistent carriers (17.8%) were identified and randomly assigned to one of four treatment groups: rifampin (600 mg once a day for 5 days), bacitracin ointment (topically applied three times a day for 10 days), combined rifampin and bacitracin, and control (no treatment). Bacitracin ointment was ineffective in eliminating S. aureus from the anterior nares and had a postreatment carrier rate equal to the control rate. Rifampin therapy caused a highly significant reduction (79%) in carriage; however, combined therapy was not as effective as treatment with rifampin alone. Of 132 strains of staphylococci isolated before and after treatment, all were susceptible to less than 0.016 micrograms of rifampin per ml. This study demonstrates that rifampin may be an effective antistaphylococcal antibiotic and could be used to control the carrier state in high-risk situations.
Pharmacokinetics and bacteriological efficacy of mezlocillin in experimental Escherichia coli and Listeria monocytogenes meningitis
Authors: Odio C , Thomas M L , McCracken G H
Published: June 2012

The purpose of this study was to determine the pharmacokinetics and bacteriological effect of mezlocillin in experimental meningitis caused by Listeria monocytogenes and two Escherichia coli strains. The half-life of mezlocillin in cerebrospinal fluid (CSF) was approximately twice that in serum of experimentally infected animals, and the penetration of drug into CSF was 5 to 15% after a single dose and 5 to 20% after continuous-infusion experiments. The bactericidal titer in CSF for both susceptible E. coli and L. monocytogenes was 1:8, whereas for the resistant E. coli strain, titers were less than 1:2 after single doses of 50 or 100 mg of mezlocillin per kg and 1:4 with continuous infusion. After single-dose and continuous-infusion experiments, the bacteriological effect of mezlocillin in experimental L. monocytogenes infections was similar to that of ampicillin. Mezlocillin reduced the colony counts of of susceptible E. coli in CSF by 90% or more after a single dose or continuous infusion but had no appreciable effect on resistant E. coli after a single dose of 50 mg/kg. In contrast, a single dose of 100 mg of mezlocillin per kg eradicated the resistant strain from CSF, despite a bactericidal titer in CSF of less than 1:2. This unexpected finding prompted us to evaluate the effect of serum on the in vitro susceptibilities of selected coliforms to mezlocillin. The activity of mezlocillin against one susceptible and four resistant strains of gram-negative, enteric bacilli was enhanced manyfold by the addition of fresh rabbit serum; this effect was abolished by heating the serum at 56 degrees C for 30 min. This interaction of mezlocillin and serum against coliform bacteria should be examined in a larger number of experimentally infected animals and in specimens obtained from mezlocillin-treated infants.
Disposition of phosphomycin in patients with pleural effusion
Authors: Lastra C F , Mariño E L , Barrueco M , Gervós M S , Gil A D
Published: June 2012

The pharmacokinetics of phosphomycin were studied in seven patients with pleural effusion of varied etiologies. All patients received a single intravenous bolus of 30 mg of antibiotic per kg. Phosphomycin levels in plasma and pleural fluid were determined simultaneously. Antibiotic levels in plasma followed a two-compartment open kinetic model. In the pleural fluid, maximum concentrations of phosphomycin, 42.63 +/- 16.03 micrograms/ml (mean +/- standard deviation), were reached at 3.69 +/- 1.08 h after administration of the antibiotic. The disappearance constant of the antibiotic from the pleural fluid was significantly smaller (0.16 +/- 0.06 h-1) than the elimination constant determined from the levels of drug in plasma (0.73 +/- 0.26 h-1). Phosphomycin persisted in antibacterial concentrations in the pleural fluid for a considerable period of time. The low accessibility of phosphomycin observed in one of the patients in the study, with a maximum concentration value of 2.16 micrograms of phosphomycin per ml of pleural fluid, could be due to the existence of pachypleuritis in that patient; this was later confirmed in clinical and histological studies done after the research described here.
In vitro comparison of Pseudomonas aeruginosa isolates with various susceptibilities to aminoglycosides and ten beta-lactam antibiotics
Authors: Wu D H , Baltch A L , Smith R P
Published: June 2012

Susceptibilities of 98 clinical isolates of Pseudomonas aeruginosa, including 33 strains with known mechanisms of amikacin resistance, were tested by the agar dilution method against 10 beta-lactam drugs. Ceftazidime, imipenem, and cefsulodin had the greatest activity, regardless of the aminoglycoside susceptibilities. The strains which were highly resistant to amikacin appeared to be less susceptible to some beta-lactam drugs, especially if their resistance was related to amikacin-inactivating enzymes; statistical significance, however, was observed for aztreonam only.
Subinhibitory concentrations of imipenem induce increased resistance to methicillin and imipenem in vitro in methicillin-resistant Staphylococcus aureus
Authors: Forbes B A , McClatchey K D , Schaberg D R
Published: June 2012

Methicillin-resistant (MR) Staphylococcus aureus that was susceptible to less than 0.75 micrograms of imipenem per ml demonstrated inducible resistance. MR S. aureus preincubated with 0.05 microgram of imipenem per ml grew in medium with an imipenem concentration of 32 micrograms/ml, and methicillin MICs increased 20-fold. Non-MR S. aureus exhibited no induction. Preincubation with methicillin produced no effect. Induction appeared to be a unique interaction of imipenem with MR S. aureus.
Phosphorylation of four acyclic guanosine analogs by herpes simplex virus type 2 thymidine kinase
Authors: Larsson A , Tao P Z
Published: June 2012

Four acyclic guanosine analogs, the (R) and (S) enantiomers of 9-(3,4-dihydroxybutyl)guanine, 9-(4-hydroxybutyl)guanine, and acyclovir were compared in enzyme kinetic experiments, using purified herpes simplex virus type 2 thymidine kinase. All four analogs showed competitive patterns of inhibition in the phosphorylation of thymidine by the viral thymidine kinase, but different affinities and relative rates of phosphorylation were observed.
Early, patient-initiated treatment of herpes labialis with topical 10% acyclovir
Authors: Spruance S L , Crumpacker C S , Schnipper L E , Kern E R , Marlowe S , Arndt K A , Overall J C
Published: June 2012

To determine whether topical acyclovir in polyethylene glycol could reduce the severity of herpes simplex labialis if applied immediately after onset of a recurrence, 10% acyclovir in polyethylene glycol ointment or polyethylene glycol alone was prospectively dispensed to 352 patients in a double-blind, randomized trial. Sixty-nine subjects initiated treatment in the prodrome (57%) or erythema (43%) stage and were followed by clinical and virological criteria. The healing time (6.0 days), maximum lesion area (42 mm2), vesicle or ulcer formation (91%), and maximum lesion virus titer (4.8 log10 PFU) in the drug recipients were not reduced in comparison with those who received the vehicle (5.2 days, 30 mm2, 75%, and 4.5 log10 PFU, respectively). Topical acyclovir in polyethylene glycol was ineffective for the treatment of herpes labialis despite an optimum therapeutic opportunity.
Tolerance percentage as a criterion for the detection of tolerant Staphylococcus aureus strains
Authors: Goessens W H , Fontijne P , van Raffe M , Michel M F
Published: June 2012

In this study, the degree of tolerance was determined in several populations of Staphylococcus aureus isolates. The degree of tolerance of a staphylococcal strain can be established in a reproducible way by exposing the strain to increasing concentrations of a beta-lactam antibiotic and determining the number of surviving bacteria at each concentration. The number of surviving bacteria was expressed as a fraction of the initial inoculum. By this technique, it appears that for each strain the value of the surviving fraction stabilized above a certain concentration of the antibiotic. This value was called the tolerance percentage of the strain. In 64 S. aureus strains isolated from blood cultures in 1982, the tolerance percentages, after exposure to methicillin, varied from less than or equal to 0.1 to 6; 28% of the strains showed a tolerance percentage of less than or equal to 0.1, and 12.5% showed a tolerance percentage of greater than or equal to 2. Similar tolerance percentages were found with cloxacillin, nafcillin, cephalothin, and penicillin. Strains with a tolerance percentage of greater than or equal to 2 showed slow killing and lysis in the presence of a high methicillin concentration. A tolerance percentage of 2 appeared to be the breakpoint between susceptible and tolerant strains. Older collections of S. aureus strains, dating from the years 1951 to 1953 and 1957 to 1958, also included strains with a survival percentage of greater than or equal to 2, thus indicating that tolerance of S. aureus to beta-lactam antibiotics is not a new phenomenon.
Elimination of plasmid pMG110 from Escherichia coli by novobiocin and other inhibitors of DNA gyrase
Authors: Hooper D C , Wolfson J S , McHugh G L , Swartz M D , Tung C , Swartz M N
Published: June 2012

The ability of novobiocin to eliminate (cure) the wild-type plasmid pMG110 from Escherichia coli has been compared with that of other inhibitors of the gyrase B subunit and of the gyrase A subunit. Novobiocin eliminated pMG110 , producing over 99% plasmid loss at concentrations two- to eightfold below the MIC for bacterial growth. Structurally related compounds ( clorobiocin , coumermycin A1, isobutyryl novenamine , and decarbamyl novobiocin) varied in their ability to eliminate pMG110 . Higher concentrations of drugs were required to eliminate pMG110 from a gyrB( Cour ) strain, implicating DNA gyrase in the curing phenomenon. For these drugs, the ratio of the concentration effecting maximal plasmid elimination to the MIC varied from 0.16 to 1.1, indicating that curing cannot be explained simply by inhibition of a pool of DNA gyrase equally available for replication of the bacterial chromosome and the plasmid DNA molecule. Inhibitors of the gyrase A subunit, nalidixic acid and oxolinic acid, eliminated pMG110 only to variable low levels. The differences in the ability of the gyrase A and B subunit antagonists to eliminate plasmids are discussed.
High-pressure liquid chromatographic assay of Bay n 7133 in human serum
Authors: Fasching C E , Hughes C E , Hector R F , Peterson L R
Published: June 2012

A high-pressure liquid chromatographic method that includes a Sep-Pak (Waters Associates, Inc., Milford , Mass.) preparation of human serum was employed for the quantitative assay of Bay n 7133. Drug levels of 0.1 to 20 micrograms/ml could be detected. No interference from amphotericin B was found in the chromatographic analysis of Bay n 7133.
Synergistic antibacterial activity between L-norvalyl-L-1-aminoethylphosphonic acid and nocardicin A
Authors: Angehrn P , Hall M J , Lloyd W J , Westmacott D
Published: June 2012

The phosphonopeptide L- norvalyl -L-1- aminoethylphosphonic acid [ Nva -Ala(P)] has been studied in combination with 12 beta-lactam antibiotics for activity against Pseudomonas aeruginosa. Nocardicin A was found to give the most potent synergistic combination with Nva -Ala(P). This interaction was widely observed in clinical isolates of P. aeruginosa in vitro and in a mouse septicemia model. Synergy was also observed in vitro and in vivo in several other species, including Proteus mirabilis, indole-positive Proteus spp., and Serratia marcescens. The interaction between Nva -Ala(P) and nocardicin A involved a strongly bacteriolytic mechanism. In addition, the individual components were complementary to one another in their action against organisms not showing synergy. These properties resulted in a broad spectrum of activity of the combination Nva -Ala(P) plus nocardicin A when used to treat experimental gram-negative bacterial infections.
Effects of furosemide, piretanide, and water loading on urinary excretion of cefazolin in humans
Authors: Morgant C , Contrepois A , Chau N P , Romaru A , Fourtillan J B , Carbon C
Published: June 2012

Antibiotics and diuretics are often prescribed concomitantly for humans. We compared the effects of two potent loop diuretics, furosemide and piretanide, with those of water loading on the urinary excretion of cefazolin. During a continuous infusion of inulin and cefazolin (10 mg/kg per h), six healthy male volunteers received a single intravenous injection of furosemide (0.3 mg/kg) or piretanide (0.1 mg/kg) or again an oral water load of 15 ml/kg over a 20-min period. In vitro, furosemide at all concentrations tested significantly reduced by about 10% the percentage of cefazolin bound to serum proteins. Piretanide exhibited such an effect only at a concentration of 2 micrograms/ml. Furosemide, piretanide, and water loading significantly and similarly increased the ratio of excreted to infused cefazolin up to 2 h after the injection of diuretic or after oral water intake. In each of the three parts of the experiment, the increase of the urinary flow rate was similar when compared with the control values. Furosemide significantly increased the cefazolin filtered load during the same time. Piretanide significantly enhanced the absolute rate of net cefazolin tubular secretion. Water loading increased the urinary excretion of cefazolin, probably through a reduction in tubular reabsorption. These results suggest that (i) furosemide and piretanide as well as water loading are capable of enhancing renal excretion of cefazolin by different complex mechanisms; (ii) cefazolin undergoes a bidirectional tubular transport; (iii) piretanide might act on the proximal tubule in addition to its main site of action on Henle's loop; and (iv) the effects of both diuretics and of water loading are unlikely to affect in vivo antibiotic activity in humans.
Single-dose amoxicillin therapy of acute uncomplicated urinary tract infections in women
Authors: Tolkoff-Rubin N E , Wilson M E , Zuromskis P , Jacoby I , Martin A R , Rubin R H
Published: June 2012

Of 210 women who were experiencing dysuria, frequent urination, pyuria, and significant bacteriuria and who were treated with a single 3-g dose of amoxicillin, 165 (79%) were cured of their original infections. Patients with infections that were negative by antibody-coated-bacteria assay were cured at a significantly higher rate than those with infections that were positive by antibody-coated-bacteria assay (90 versus 59%; P less than 0.001). Similarly, those with infections caused by amoxicillin-susceptible organisms were cured at a significantly higher rate than those with infections caused by resistant organisms (85 versus 50%; P less than 0.001). Of 27 patients who had infections caused by amoxicillin-susceptible organisms and who had relapses after single-dose therapy, 14 (52%) had relapses again after a conventional 10-day course of therapy, although all responded to a 6-week course. An additional 27 patients experiencing dysuria, frequent urination, and pyuria but who had a lower number of uropathogens in the urine (10(2) to 10(4.5)/ml of urine) were treated with single-dose therapy, with a 100% eradication of organisms and an 89% rate of symptomatic relief.
Comparative efficacies of pivmecillinam and ampicillin in acute shigellosis
Authors: Kabir I , Rahaman M M , Ahmed S M , Akhter S Q , Butler T
Published: June 2012

The clinical efficacies of pivmecillinam and ampicillin were compared in a randomized double-blind trial in the treatment of acute shigellosis. Of 44 adult male patients, all culture positive for Shigella strains, 22 patients received 400 mg of pivmecillinam and 22 patients received 500 mg of ampicillin every 6 h. Both drugs were administered orally for 5 days. Four patients receiving ampicillin were infected with Shigella strains that were resistant to ampicillin but susceptible to pivmecillinam, and two patients receiving pivmecillinam were infected with Shigella strains resistant to both ampicillin and pivmecillinam. The mean duration of diarrhea in all patients receiving pivmecillinam was 3.3 days compared with 4.5 days in patients receiving ampicillin (P less than 0.05). When patients infected with the resistant strains were excluded, the mean duration of diarrhea in patients receiving pivmecillinam was 3.2 days compared with 4.1 days in patients receiving ampicillin. The patients infected with strains susceptible to both antibiotics had mean durations of fecal excretion of Shigella strains of 1.2 days for those treated with pivmecillinam and 1.4 days for those treated with ampicillin. The patients infected with organisms resistant to both drugs had longer durations of diarrhea and fecal excretion of Shigella strains. The results suggest that pivmecillinam is as effective as ampicillin and can be a useful drug for the treatment of shigellosis.
Enhancement of copper toxicity by siderophores in Bacillus megaterium
Authors: Arceneaux J E , Boutwell M E , Byers B R
Published: June 2012

Chelation of copper by siderophores enhanced the toxicity of copper for Bacillus megaterium. Although this antibacterial activity appeared to be rapidly bactericidal, it could be partly reversed by addition of deferrisiderophore , or of ferrisiderophore at high concentration, immediately after exposure of cells to the cupric-siderophore complex.
Sulfamethoxazole-trimethoprim-resistant Shigella flexneri in northeastern Brazil
Authors: Tiemens K M , Shipley P L , Correia R A , Shields D S , Guerrant R L
Published: June 2012

In contrast to prior experience in northeastern Brazil, three of four Shigella flexneri strains recently isolated from patients with acute inflammatory diarrhea in this setting were found to be resistant to sulfamethoxazole-trimethoprim. The resistant strains contained large, different plasmids, two of which were transferred with sulfamethoxazole-trimethoprim resistance to Escherichia coli K-12 recipient strains.
Susceptibility studies of multiply resistant Haemophilus influenzae isolated from pediatric patients and contacts
Authors: Campos J , Garcia-Tornel S , Sanfeliu I
Published: June 2012

From February 1981 to December 1983, 225 strains were isolated from pediatric patients infected with Haemophilus influenzae. Forty-one strains were found to be resistant to ampicillin, chloramphenicol, and other antibiotics. They were isolated from 20 patients with invasive diseases (meningitis, 16; bacteremia, 4) and 21 with noninvasive diseases (otitis media, 19; conjunctivitis, 2). During this period, 44 patients with invasive diseases were seen (meningitis, 28; bacteremia, 16). Strains resistant to both ampicillin and chloramphenicol occurred in 45.4% of cerebrospinal fluid and blood isolates and in 51% of cerebrospinal fluid isolates only. In this group, individual resistance to ampicillin was 50%; chloramphenicol, 52.2%; tetracycline, 54.5%; and sulfamethoxazole-trimethoprim, 63.6%. No epidemiological relationship could be found among the patients. The presence of asymptomatic carriers was investigated in two nurseries and in eight family groups. From a total of 125 individuals studied, 80 were found to be colonized by H. influenzae, and 36 carried multiply resistant strains. From patients and carriers, 77 strains were found to be resistant to ampicillin, chloramphenicol, and other drugs; 39 belonged to type b (cerebrospinal fluid, 16; blood, 4; ear, 7; and nasopharynx, 12), and 38 were non-type b. The most frequent pattern of resistance was ampicillin-chloramphenicol-tetracycline-sulfamethoxazole-trimethoprim (94.8%), followed by ampicillin-chloramphenicol-tetracycline (3.9%). The disk diffusion method correctly predicted multiple resistance. The mean inhibition zone diameters were: ampicillin, 12.8 mm; chloramphenicol, 15.2 mm; tetracycline, 9.9 mm; and sulfamethoxazole-trimethoprim, 10.8 mm. These resistant strains were susceptible to cefotaxime, moxalactam, cefoperazone, cefuroxime, rifampin, and gentamicin. Our data suggest that in Spain the resistance of H. influenzae to ampicillin and chloramphenicol is endemic and that other effective therapeutic modalities are needed.
Enhanced in vitro bactericidal activity of amikacin or gentamicin combined with three new extended-spectrum cephalosporins against cephalothin-resistant members of the family Enterobacteriaceae
Authors: Bayer A S , Eisenstadt R , Morrison J O
Published: June 2012

The in vitro bactericidal interactions of three new extended-spectrum cephalosporins (ceftriaxone, ceftizoxime, or ceftazidime) in combination with gentamicin or amikacin were compared against 40 recent nosocomial bloodstream Enterobacteriaceae isolates by the timed-kill curve technique. All of the study strains were cephalothin resistant, and 56% were resistant to cefamandole. Combinations of aminoglycosides plus ceftriaxone or ceftizoxime exhibited an enhanced bactericidal effect with the highest frequency (approximately 85 to 90%), whereas gentamicin-ceftazidime combinations demonstrated the lowest frequency (for 60% of assays, P less than 0.0005 against the nonceftazidime regimens). The enhanced bactericidal effects occurred within readily achievable drug levels in serum for all of the single antibiotic constituents. No bactericidal antagonism was observed. There was no discernible relationship between the relative in vitro susceptibilities of the 40 study isolates to ceftazidime and the potential for gentamicin-ceftazidime combinations to demonstrate enhanced bactericidal activity. In 14 of the 40 study strains (35%) all six drug combinations tested demonstrated an enhanced bactericidal effect. In nearly 50% of bactericidal interactions which resulted in enhanced bactericidal effect at 24 h, such enhanced killing was clearly demonstrable by 4 h of incubation. These results delineate a frequent and rapid enhancement of in vitro bactericidal activity between three new extended-spectra cephalosporins and aminoglycosides against nosocomial members of the family Enterobacteriaeceae.
Mechanism of resistance of an ampicillin-resistant, beta-lactamase-negative clinical isolate of Haemophilus influenzae type b to beta-lactam antibiotics
Authors: Parr T R , Bryan L E
Published: June 2012

The mechanism of non-beta-lactamase-mediated beta-lactam resistance in a clinical isolate of Haemophilus influenzae type b was studied. This clinical isolate showed up to a 32-fold increase in MICs of a wide variety of beta-lactams, including moxalactam and cefotaxime, although no beta-lactamase activity was detected, even after attempted induction. Transformation of broad-spectrum beta-lactam resistance into ampicillin-susceptible H. influenzae RDnov was accomplished. Examination of the outer membrane protein profile of the resistant parent by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of Triton X-100-extracted membranes revealed an unusual major outer membrane protein band at a molecular weight of 45,000. This outer membrane protein profile did not transform with beta-lactam resistance. Permeability differences were noted between the resistant strain and the nonisogenic susceptible strain of H. influenzae, although these penetration differences were not transformed. Comparison of the penicillin-binding protein profile of a resistant transformant with that of a susceptible parent with both whole-membrane preparations and whole-cell labeling, revealed a major reduction in binding affinity to penicillin-binding proteins 3a and 3b (molecular weights, 68,000 and 65,000, respectively). Thus, alteration in penicillin-binding proteins 3a and 3b correlated with the beta-lactam resistance.
Susceptibility of anaerobic bacteria from several French hospitals to three major antibiotics
Authors: Dubreuil L , Devos J , Neut C , Romond C
Published: June 2012

The in vitro activity of cefoxitin was compared with those of metronidazole and clindamycin against 322 strains of anaerobic bacteria collected from several hospitals during 1982 and tested by an agar dilution method. Metronidazole and cefoxitin inhibited at least 89% of strains tested, whereas clindamycin was less active.