bluuebunny/crossref_metadata_2025 huggingface dataset:
Carumonam (Ro 17-2301; AMA-1080) compared with gentamicin for treatment of complicated urinary tract infections
Authors: Hoepelman A I , Bakker L J , Verhoef J
Published: June 2012

Carumonam and gentamicin were compared in a prospective, randomized study of 52 patients with complicated urinary tract infections. Patients were treated with either carumonam (1 g every 8 h) or gentamicin (1 mg/kg every 8 h). The mean duration of therapy (carumonam, 8.5 days; gentamicin, 8.5 days) was similar for both groups. A total of 45% of patients treated with carumonam and 48% of those receiving gentamicin were cured, as defined by a negative culture 1 to 2 weeks after therapy. After 4 to 6 weeks, the figures were 27% for carumonam and 38% for gentamicin. In the carumonam group, there were 6 relapses and 11 reinfections. In the gentamicin group, there were eight relapses and five reinfections. Adverse effects in the carumonam group were limited to phlebitis at the intravenous infusion site in two patients; another patient developed bloody diarrhea. Nephrotoxicity was documented in two patients in the gentamicin treatment group (9%), and another patient developed minor liver function disturbances. Three patients with gentamicin-resistant carumonam-susceptible isolates were treated with carumonam, and two were cured. Urinary colonization with group D streptococci occurred in 7 of 27 (26%) carumonam-treated patients compared with 7 of 19 (37%) gentamicin-treated patients; no one required treatment. A significant correlation was found between colonization with group D streptococci and neurogenic bladder dysfunction (P less than 0.007). It is concluded that the use of the carumonam is as effective as the gentamicin regimen in the treatment of complicated urinary tract infections.
Effect of phosphorylated ribavirin on vesicular stomatitis virus transcription
Authors: Toltzis P , O'Connell K , Patterson J L
Published: June 2012

The effect of phosphorylated ribavirin on a vesicular stomatitis virus (VSV) in vitro transcription reaction was examined. Viral mRNA synthesized in the presence of the 5' mono-, di-, and triphosphorylated forms of the drug translated with equal efficiencies under the test conditions. However, all three phosphorylated species inhibited VSV transcription. The mono- and diphosphorylated forms of the drug possessed approximately two to three times the inhibitory activity as the triphosphorylated form. Transcripts synthesized in the presence of drug were full length and were absent of incorporated drug. Inhibition by ribavirin 5'-diphosphate could be reversed by the addition of UTP, CTP, and GTP, while the addition of GDP to the reaction did not reverse inhibition. Ribavirin diphosphate was added to a La Crosse virus in vitro transcription assay to determine whether an inhibitory effect could be established in a viral system that was more sensitive to ribavirin than was VSV; it led to profound inhibition of RNA synthesis at concentrations as low as 0.1 microgram/ml. These data suggest that ribavirin has an effect on the initial steps of transcription by some RNA-dependent RNA polymerases and that this effect may be mediated by several phosphorylated forms.
Effect of norfloxacin on theophylline pharmacokinetics at steady state
Authors: Bowles S K , Popovski Z , Rybak M J , Beckman H B , Edwards D J
Published: June 2012

Norfloxacin is a currently marketed fluoroquinolone antibiotic. Other quinolones which are structurally similar to norfloxacin, particularly enoxacin, inhibit theophylline clearance. Since norfloxacin may be administered to patients also receiving theophylline, we studied the effect of norfloxacin on the pharmacokinetics of theophylline in 10 healthy male volunteers. A randomized, crossover study design with a 2-week washout period between treatments was used. Subjects received oral theophylline (200 mg of aminophylline [theophylline ethylenediamine]) three times daily for 4 days either alone or with 400 mg of norfloxacin (orally) twice daily for the same period. Theophylline concentrations in serum were significantly higher (P less than 0.05) at 0, 3, 4, 10, and 12 h following the final dose in the norfloxacin treatment group than in the group receiving only theophylline. However, mean theophylline oral clearance was not significantly different between the two treatments (2.85 +/- 0.68 liters/h without norfloxacin versus 2.56 +/- 0.53 liters/h with norfloxacin [P = 0.08]). Similarly, no significant differences were observed in theophylline half-life (P = 0.11). We conclude that norfloxacin is unlikely to have a clinically significant effect on theophylline disposition in most patients.
Plasmids and pheromone response of the beta-lactamase producer Streptococcus (Enterococcus) faecalis HH22
Authors: Murray B E , An F Y , Clewell D B
Published: June 2012

Streptococcus (Enterococcus) faecalis HH22 is a clinical isolate that produces beta-lactamase and is resistant to various other antimicrobial agents. In this study, HH22 was found to contain three conjugative plasmids and a conjugative transposon. pBEM10 encodes beta-lactamase, gentamicin resistance, and a response to the peptide pheromone cAD1; pAM323 encodes erythromycin resistance; and pAM324 encodes no known resistance. The latter two plasmids respond to pheromones designated cAM323 and cAM324 which are unrelated to other previously characterized pheromones. pBEM10 and pAM323 are the second and third examples of naturally occurring R plasmids that confer a sex pheromone response.
Ampicillin concentrations in human dental granuloma after a single oral administration of talampicillin
Authors: Akimoto Y , Nishimura H , Komiya M , Kaneko K , Fujii A , Tamura T
Published: June 2012

Ampicillin concentrations in human serum and dental granulomas of 31 patients were determined after a single oral dose of talampicillin (equivalent to 500 mg of ampicillin) was administered to each. The specimens were taken at 1.5, 2.0, 2.5, 3.0, and 3.5 h after the administration of talampicillin. The mean peak ampicillin concentrations in serum and dental granulomas occurred at identical times, 2.5 h, and were 8.29 micrograms/ml (range, 1.81 to 13.20 micrograms/ml) and 2.94 micrograms/g (range, 1.14 to 7.16 micrograms/g), respectively. The mean dental granuloma/serum ampicillin concentration ratio at the peak time (2.5 h) was 0.42 (range, 0.29 to 0.56). Ampicillin concentrations in dental granulomas exceeded most of the MICs for the bacteria commonly isolated from odontogenic infection.
Activity of trospectomycin against Bacteroides fragilis and other Bacteroides species
Authors: Jacobus N V , Tally F P
Published: June 2012

The in vitro activity of trospectomycin (U-63366; 6'-n-propyl spectinomycin pentahydrate sulfate) was evaluated against 189 clinical isolates of the Bacteroides fragilis group and 65 Bacteroides species isolates. At less than or equal to 8 micrograms/ml, the activity of trospectomycin compared favorably with those of clindamycin and cefoxitin against B. fragilis, Bacteroides distasonis, and Bacteroides vulgatus, and there was no cross resistance to these three drugs among the strains of the B. fragilis group. All the Bacteroides species were susceptible to trospectomycin. The results of this in vitro study indicate that trospectomycin possesses excellent activity against Bacteroides species.
Pilot study of recombinant interferon alpha-2a for treatment of infants with bronchiolitis induced by respiratory syncytial virus
Authors: Portnoy J , Hicks R , Pacheco F , Olson L
Published: June 2012

Eleven children with bronchiolitis induced by respiratory syncytial virus received 10,000 to 70,000 U of recombinant interferon alpha-2a per kg of body weight per day. None developed signs of toxicity, and all but one developed an antiviral state following treatment. Interferon alpha-2a appears to be safe for infants with bronchiolitis. Its efficacy for the treatment of this condition remains to be determined.
Influence of food on bioavailability of amdinocillin pivoxil
Authors: Bornemann L D , Castellano S , Lin A H , Enthoven D , Patel I H
Published: June 2012

The bioavailability of amdinocillin was not altered when amdinocillin pivoxil was ingested 1 h before a standard breakfast, and it increased by 20% when amdinocillin pivoxil was ingested with or 1 h after a standard breakfast. Amdinocillin pivoxil would be convenient for patients since it may be taken with or without food.
In vitro susceptibility of Bacillus spp. to selected antimicrobial agents
Authors: Weber D J , Saviteer S M , Rutala W A , Thomann C A
Published: June 2012

Although often dismissed as contaminants when isolated from blood cultures, Bacillus spp. are increasingly recognized as capable of causing serious systemic infections. As part of a clinical-microbiological study, 89 strains of Bacillus spp. isolated from clinical blood cultures between 1981 and 1985 had their species determined and were tested for antimicrobial agent susceptibility to 18 antibiotics. Species of isolates were determined by the API 50CH and API 20E systems. Bacillus cereus (54 strains) was the most common species isolated, followed by B. megaterium (13 strains), B. polymyxa (5 strains), B. pumilus (4 strains), B. subtilis (4 strains), B. circulans (3 strains), B. amyloliquefaciens (2 strains), B. licheniformis (1 strain), and Bacillus spp. (3 strains). Microdilution MIC susceptibility tests revealed all B. cereus strains to be susceptible to imipenem, vancomycin, chloramphenicol, gentamicin, and ciprofloxacin. Non-B. cereus strains were most susceptible to imipenem, vancomycin, LY146032, and ciprofloxacin. Disk susceptibility testing suggested that B. cereus was rarely susceptible to penicillins, semisynthetic penicillins, or cephalosporins with the exception of mezlocillin. In contrast, many non-B. cereus strains were susceptible to penicillins, semisynthetic penicillins, and cephalosporins, but marked variability was noted among species.
Fluconazole and testosterone: in vivo and in vitro studies
Authors: Hanger D P , Jevons S , Shaw J T
Published: June 2012

Fluconazole (UK-49,858), a novel bis-triazole antifungal agent, was given orally to groups of 10 male volunteers at doses of 25 and 50 mg/day for 28 days. Blood samples for testosterone estimation were taken from these and from a placebo group at several time points on days 1, 14, and 28 of the study, and the assay results demonstrated that the compound had no significant effect on circulating testosterone levels. Similarly, in studies with rat Leydig cells in vitro, fluconazole at concentrations up to 10 micrograms/ml was found to be only a weak inhibitor of testosterone production, whereas ketoconazole caused more than 50% inhibition at 0.1 microgram/ml. It is concluded that fluconazole, in contrast to ketoconazole, has little effect on the biosynthesis of testosterone by mammalian cells.
Enhanced binding of polycationic antibiotics to lipopolysaccharide from an aminoglycoside-supersusceptible, tolA mutant strain of Pseudomonas aeruginosa
Authors: Rivera M , Hancock R E , Sawyer J G , Haug A , McGroarty E J
Published: June 2012

The lipopolysaccharide (LPS) of the aminoglycoside-supersusceptible Pseudomonas aeruginosa tolA mutant PAO1715 was compared with its parent strain PAO1670 and tol+ revertant PAO1716. Electrophoretic separation of purified LPSs from the three isolates showed similar LPS banding patterns. Analysis of the Western blots of these LPSs from the three isolates with O-antigen-specific monoclonal antibody indicated that the ladder pattern consisted of doublet bands, which presumably reflected a modification of core or lipid A; the level of one of the bands in the doublet was in much lower amounts in the isolate from the tolA mutant than in that from the parent or revertant. Results of competitive displacement experiments, in which the cationic spin probe 4-dodecyldimethylammonium-1-oxyl-2,2,6,6-tetramethylpiperidine bromide was displaced from its LPS-binding site by polycations, revealed that the tolA mutant had a much higher affinity for gentamicin, polymyxin, Ca2+, and Mg2+ than did the parent or revertant. The order of affinity for all samples was polymyxin B much greater than gentamicin C much greater than Ca2+ greater than Mg2+. Both gentamicin and polymyxin induced rigidification of all of the LPS samples, but for the sample from the tolA mutant, rigidification occurred at substantially lower concentrations. Dansyl polymyxin titration experiments with intact cells demonstrated that the increased affinity of the LPS from the tolA mutant for polycations was reflected in an increase in the affinity of binding to the cell. Together these data suggest that the tolA mutant is supersusceptible to aminoglycosides by virtue of an LPS change which increases the binding affinity of the LPS for polycations, including gentamicin.
In vitro activity of lomefloxacin (SC-47111; NY-198), a difluoroquinolone 3-carboxylic acid, compared with those of other quinolones
Authors: Chin N X , Novelli A , Neu H C
Published: June 2012

Lomefloxacin (SC-47111; NY-198) is a new difluoroquinolone agent. It inhibited 90% of Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Proteus mirabilis, Morganella morganii, Proteus vulgaris, Serratia marcescens, Salmonella spp., Shigella spp., Aeromonas spp., Yersinia spp., Haemophilus influenzae, and Neisseria gonorrhoeae at less than or equal to 2 micrograms/ml. Lomefloxacin inhibited 90% of Pseudomonas aeruginosa at 4 micrograms/ml. Lomefloxacin was equal in activity to norfloxacin against Escherichia coli, Klebsiella spp., Enterobacter spp., Haemophilus influenzae, and Neisseria gonorrhoeae but was twofold less active against Proteus spp., Providencia spp., Serratia marcescens, Salmonella spp., and Shigella spp. Ofloxacin was generally 2- to 4-fold more active, and ciprofloxacin was 4- to 16-fold more active. Lomefloxacin inhibited Staphylococcus aureus, including methicillin-resistant isolates, but MICs for 90% of streptococcal species tested were 8 micrograms/ml. In the presence of 9 mM Mg2+, MICs for Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa were increased, as they were when they were tested in urine. A single-step increase in resistance to eightfold above the MIC occurred at a frequency of less than 10(-10), but serial transfer of bacteria in the presence of the agent produced MIC increases. Lomefloxacin had activity and properties comparable to those of many of the new quinolones.
In vitro activity of an oral iminomethoxy aminothiazolyl cephalosporin, R-3746
Authors: Chin N X , Neu H C
Published: June 2012

The in vitro activity of R-3746, an iminomethoxy aminothiazolyl cephalosporin with a CH2OCH3 moiety at position 3, was compared with those of other antibiotics. R-3746 inhibited the majority of hemolytic streptococci (groups A, B, C, F, and G) and Streptococcus pneumoniae at less than 0.06 micrograms/ml, which was comparable to the activity of amoxicillin, 2- to 8-fold more active than cefixime, and 16- to 64-fold more active than cefaclor and cephalexin. Ninety percent of beta-lactamase-producing Haemophilus influenzae and Neisseria gonorrhoeae were inhibited at a concentration 0.25 micrograms/ml, but it was less active against Branhamella spp. It did not inhibit (MIC, greater than 16 micrograms/ml) enterococci, viridans group streptococci, or methicillin-resistant staphylococci. The MICs of R-3746 for 90% of strains tested for Escherichia coli; Klebsiella pneumoniae; Citrobacter diversus; Proteus mirabilis; and Salmonella, Shigella, and Yersinia spp. were less than or equal to 1 micrograms/ml. It was two- to eightfold less active than cefixime but was markedly superior to cefaclor, cephalexin, amoxicillin-clavulanate, and trimethoprimsulfamethoxazole. R-3746 inhibited 50% of Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii, Morganella spp., Providencia spp., Proteus vulgaris, and Serratia marcescens at less than or equal to 8 micrograms/ml. Pseudomonas spp. were resistant. Fifty percent of Clostridium spp. were inhibited by 0.5 micrograms/ml, but MICs for Bacteroides spp. were greater than 128 micrograms/ml. R-3746 was not appreciably hydrolyzed by most chromosomal and plasmid-mediated beta-lactamases.
Aminoglycoside resistance among Pseudomonas aeruginosa isolates with an unusual disk diffusion antibiogram
Authors: Clark R B , Sanders C C , Pakiz C B , Hostetter M K
Published: June 2012

In recent years, a number of clinical microbiology laboratories have isolated Pseudomonas aeruginosa with the unusual aminoglycoside disk diffusion result of resistance to both amikacin and gentamicin but susceptibility to tobramycin (ArGrTs). A total of 39 isolates of P. aeruginosa reported to have this resistance pattern were retested by the standard National Committee for Clinical Laboratory Standards disk diffusion procedure; 30 strains (77%) were confirmed to be ArGrTs. These 30 isolates were further examined for susceptibility to those aminoglycosides by agar dilution and broth micro- and macrodilution methods. Only 27, 27, and 23% of the isolates appeared to be ArGrTs by agar, broth microdilution, and broth macrodilution testing, respectively. Most of the remaining isolates were resistant to all three aminoglycosides when tested by broth dilution and resistant only to gentamicin when tested by agar dilution. The percentages of strains resistant to any particular aminoglycoside by agar dilution, broth microdilution, and broth macrodilution, respectively, were 43, 80, and 70 for amikacin, 97, 93, and 100 for gentamicin, 100, 100, and 100 for netilmicin, 30, 87, and 93 for sisomicin, and 13, 57, and 50 for tobramycin. These results indicate that strains showing the unusual aminoglycoside antibiogram are less susceptible to aminoglycosides in general and should probably be considered borderline resistant to all aminoglycosides. The efficacy of aminoglycosides in the treatment of infections produced by these strains is unknown.
Role of cell defense against oxidative damage in the resistance of Candida albicans to the killing effect of amphotericin B
Authors: Sokol-Anderson M , Sligh J E , Elberg S , Brajtburg J , Kobayashi G S , Medoff G
Published: June 2012

A laboratory-derived mutant of Candida albicans B311 (L) and a clinical isolate (C) of C. albicans, both lacking membrane ergosterol, were less susceptible to amphotericin B (AmB)-induced cell membrane permeability to K+ and lethality than was the wild-type laboratory strain (B311) which contained ergosterol. The resistance of L and C to AmB-induced killing was much greater than the level of resistance to AmB-induced cell membrane permeability. L and C were also less susceptible to killing by H2O2 than was B311, and when treated with menadione, they each produced less H2O2 than did B311. In addition, their levels of catalase activity were 3.8-fold (L) and 2-fold (C) higher than that of B311. The ergosterol deficiency in L and C probably impaired AmB binding to the cells, thereby lowering AmB effectiveness as measured by both cell membrane permeability and killing. Resistance of strains L and C to oxidation-dependent damage likely contributed to a diminished response to AmB-induced lethality.
Evaluation of 500- and 1,000-mg doses of ciprofloxacin for the treatment of chancroid
Authors: Bodhidatta L , Taylor D N , Chitwarakorn A , Kuvanont K , Echeverria P
Published: June 2012

A randomized, double-blind study was performed comparing ciprofloxacin in a 500-mg single dose with 1,000 mg (500-mg doses given 12 h apart) for the treatment of chancroid in Thailand. Haemophilus ducreyi was isolated from 87 (48%) of 180 men with a clinical diagnosis of chancroid. For men with ulcers that were culture positive for H. ducreyi, rates of cure were 100% in the 500-mg group and 98% in the 1,000-mg group. For men with ulcers that were culture negative for H. ducreyi, rates of cure were 93% in the 500-mg group and 96% in the 1,000-mg group. The MIC of ciprofloxacin for 50% of isolates among 85 isolates of H. ducreyi was 0.007 micrograms/ml (range, 0.002 to 0.03 micrograms/ml). No significant adverse effects were detected in either group. These data indicate that both of these treatment regimens are equally effective therapies for chancroid in Thailand.
Multiple-dose pharmacokinetics of intravenously administered cefoperazone and sulbactam when given in combination to infected, seriously ill, elderly patients
Authors: Schwartz J I , Jauregui L E , Bachmann K A , Martin M E , Reitberg D P
Published: June 2012

The pharmacokinetics of cefoperazone and sulbactam in combination were evaluated in six, elderly, seriously ill patients treated with the drug combination for intra-abdominal infections. After giving informed consent, three males and three females aged 63.5 to 77.5 (mean 67.9) years and weighing 54.5 to 86.8 (mean, 67.6) kg were treated with cefoperazone (2.0 g) and sulbactam (1.0 g) infused intravenously every 12 h for at least 5 days. Cefoperazone and sulbactam pharmacokinetics were characterized on both days 1 and 5 of treatment. Eleven serial blood samples were obtained just prior to and following dose 1 on days 1 and 5 of treatment. Mean estimates of cefoperazone maximal concentration in plasma (Cmax), area under the curve of drug concentration in plasma versus time (AUC), half-life (t 1/2), apparent volume of distribution by the area method (Varea), apparent volume of distribution at steady state (Vss), and total body clearance (CL) for day 1 (day 5) were 297.5 237.5) micrograms/ml, 1,247 (1,063) micrograms.h/ml, 7.0 (4.9) h, 16.1 (13.4) liter, 13.1 (14.4) liter, and 28.9 (34.2) ml/min, respectively. Day 1 (day 5) mean values for sulbactam Cmax, AUC, t 1/2, Varea, Vss, and CL were 110.3 (78.0) micrograms/ml, 228 (217) micrograms.h/ml, 3.4 (2.5) h, 26.1 (18.5) liter, 18.9 (15.4) liter, and 97 (94) ml/min, respectively. Both drugs evidenced slower elimination and greater pharmacokinetic variability in these patients compared with values previously reported for normal volunteers. As patients improved during the course of therapy, the only pharmacokinetic parameter significantly changed between days 1 and 5 was a shortened sulbactam t 1/2. Our inability to find substantial evidence of pharmacokinetic normalization may have been related to sample size and study duration. Both drugs were present in potentially therapeutic concentrations for the entire 12-h dosing interval, but without undue accumulation from days 1 to 5.
Azithromycin, a macrolide antibiotic with potent activity against Toxoplasma gondii
Authors: Araujo F G , Guptill D R , Remington J S
Published: June 2012

Doses of 200 mg of azithromycin per kg (body weight) administered by the oral route daily for 10 days completely protected mice against death caused by intraperitoneal infection with Toxoplasma gondii. The same treatment regimen also protected 80% of mice infected intracerebrally, which suggests that azithromycin attains active concentrations in the inflamed central nervous system.
Animal model for evaluating the convulsive liability of beta-lactam antibiotics
Authors: Williams P D , Bennett D B , Comereski C R
Published: June 2012

The beta-lactam antibiotics imipenem-cilastatin, BMY-26225, and cefazolin significantly lowered the convulsive threshold of pentylenetetrazole in mice. In addition, imipenem-cilastatin and cefazolin were found to inhibit 3H-labeled gamma-aminobutyric acid binding to synaptic membranes from rat brains. Our results suggest that the pentylenetetrazole convulsive model may be useful in evaluating the proconvulsive liabilities of new carbapenems and other beta-lactam antibiotics and that the mechanism of imipenem-cilastatin and cefazolin toxicity may involve interaction with gamma-aminobutyric acid receptors.
Ribavirin small-particle-aerosol treatment of influenza B virus infection
Authors: Bernstein D I , Reuman P D , Sherwood J R , Young E C , Schiff G M
Published: June 2012

In a randomized double-blind trial of aerosolized ribavirin for the treatment of influenza B virus infection, no significant difference was found in the febrile course or symptom score of the ribavirin-treated versus placebo-treated patients. The apparent lack of efficacy in this study as compared with that in previous studies is unexplained.
Radiochemical method for evaluating the effect of antibiotics on Escherichia coli biofilms
Authors: Dix B A , Cohen P S , Laux D C , Cleeland R
Published: June 2012

A simple radiochemical method for evaluating the action of antibiotics on Escherichia coli cells in biofilms is reported. After growth, biofilms of E. coli ATCC 25922 on disks of urinary catheter material were suspended in fresh medium containing or lacking an antibiotic, incubated for 4 h at 37 degrees C, and pulse-labeled with [3H]leucine for 5 min. Radioactivity in trichloracetic acid-precipitable material in the biofilm and in the surrounding medium (planktonic E. coli) was then measured. Antibiotic-induced inhibition of incorporation of [3H]leucine into the cells in the biofilm was far less pronounced than incorporation into planktonic cells and, furthermore, correlated well with loss in viable counts. The method is simple, inexpensive, and extremely timesaving.
Treatment of uncomplicated gonorrhea with single-dose imipenem-cilastatin
Authors: Verdon M S , Judson F N , Ehret J M , Root C J , Hook E W , McCormack W M , Frances C A , Draft K , Shands J W , Handsfield H H
Published: June 2012

Single 500-mg intramuscular doses of imipenem-cilastatin cured 116 (95%) of 122 men and 9 of 9 women with uncomplicated gonorrhea due to beta-lactamase-negative Neisseria gonorrhoeae. Most co-existing Chlamydia trachomatis infections persisted. Imipenem-cilastatin is effective for uncomplicated gonorrhea in men but has no advantages over other available regimens.
Vancomycin pharmacokinetics in patients with various degrees of renal function
Authors: Rodvold K A , Blum R A , Fischer J H , Zokufa H Z , Rotschafer J C , Crossley K B , Riff L J
Published: June 2012

The influence of age, protein binding, and renal function on the pharmacokinetics of intravenous vancomycin was evaluated in 37 adult patients with various degrees of renal function. Patients were categorized into three groups based on measured creatinine clearance (CLCR): groups 1, 2, and 3 had 24-h CLCRs of greater than 70, 40 to 70, and 10 to 39 ml/min per 1.73 m2, respectively. After 1 h of intravenous infusion, concentrations of vancomycin in serum declined in a biexponential manner in all patients. Diminished renal function in groups 2 and 3 was accompanied by a lower total body vancomycin clearance (CL) (52.6 and 31.3, respectively, versus 98.4 ml/min per 1.73 m2) and a lower renal vancomycin clearance (CLR) (48.2 and 19.8, respectively, versus 88.0 ml/min per 1.73 m2) than in group 1. No significant differences in apparent distribution volume of the central compartment or apparent distribution volume at steady state were observed. Mean serum protein binding of vancomycin was 30% and was not significantly affected by renal function. Stepwise multiple linear regression analysis revealed that CLCR was the strongest predictor of vancomycin CL (r = 0.77, P less than 0.001) and vancomycin CLR (r = 0.87, P less than 0.001). Age did not significantly improve these correlations once CLCR was included. The relationship of vancomycin CL and CLCR was utilized to develop the following equation to dose vancomycin in the majority of renally impaired patients: dose (milligrams per kilogram per 24 h) = 0.227CLCR + 5.67, where CLCR is standardized to milliliters per minute per 70 kg. The practical dosing intervals that the calculated dose can be divided into and administered include 8, 12, 24, and 48 h based on the CLCR of the patient.
Prospective cost analysis of moxalactam versus clindamycin plus gentamicin for endomyometritis after cesarean section
Authors: Knodel L C , Goldspiel B R , Gibbs R S
Published: June 2012

The direct and indirect costs associated with either moxalactam or clindamycin plus gentamicin as treatment for endomyometritis after emergent cesarean section were compared in an open, randomized prospective trial of 114 patients. A total of 58 patients were assigned to receive moxalactam, 2 g intravenously (i.v.) every 8 h for 5 doses, followed by 2 g every 12 h and prophylactic vitamin K (10 mg) intramuscularly, and 56 patients were assigned to receive clindamycin (600 mg) i.v. every 6 h plus gentamicin (1.5 mg/kg) i.v. every 8 h. Prothrombin times were measured in moxalactam-treated patients, and patients treated with clindamycin plus gentamicin had urinalyses and blood urea nitrogen and serum creatinine determinations performed before and after treatment. Also, gentamicin levels in serum were determined as clinically indicated. A satisfactory treatment response was defined as the resolution of signs and symptoms of endomyometritis within 3 days of the start of antibiotic therapy. Satisfactory responses were demonstrated in 78% of the moxalactam-treated patients and 84% of patients treated with clindamycin plus gentamicin. Mean hospital costs for laboratory tests ($30.30 versus $4.53) and mean patient charges for laboratory tests ($76.39 versus $27.81) and medications ($539.45 versus $421.82) were significantly higher in patients treated with clindamycin plus gentamicin (P less than 0.05), while mean medication costs to the hospital were greater in the moxalactam group ($255.47 versus $195.68; P less than 0.05). However, total patient charges and total hospital drug-associated costs were not significantly different for the two group. In this tudy, moxalactam was similar in efficacy and, despite its higher acquistion cost, was comparable in total hospital costs and patient charges to clindamycin plus gentacmicin in treating endomyometritis.
Susceptibilities to antibiotics and antiseptics of new species of the family Enterobacteriaceae
Authors: Freney J , Husson M O , Gavini F , Madier S , Martra A , Izard D , Leclerc H , Fleurette J
Published: June 2012

One hundred and sixty-nine strains of new species of the family Enterobacteriaceae, isolated mainly from the environment, were tested to determine their susceptibilities to 13 antibiotics and 4 antiseptics or disinfectants. All the species were susceptible to aminoglycosides, doxycycline, and trimethoprim but were resistant to chloramphenicol. Susceptibility to beta-lactams varied more among the strains. However, all the strains were cefotaxime susceptible, apart from some Buttiauxella agrestis strains for which MICs were greater than 256 micrograms/ml. The antiseptic MBCs were similar to those published elsewhere for species of the Enterobacteriaceae of clinical origin. No resistance to chlorhexidine was observed. On the other hand, the environmental strains presented a greater resistance to active chlorine than did the reference strains.
Daptomycin (LY146032) treatment of experimental enterococcal endocarditis
Authors: Bush L M , Boscia J A , Kaye D
Published: June 2012

This study compared daptomycin (LY146032) with penicillin G procaine and vancomycin without and with gentamicin for treatment of experimental enterococcal endocarditis. The strain of Streptococcus (Enterococcus) faecalis used in this study was killed by daptomycin in vitro in broth but not in serum. In rabbits treated for 3 days, daptomycin significantly reduced bacterial counts of vegetations compared with no therapy but was significantly less effective than penicillin G procaine or vancomycin. Daptomycin-gentamicin significantly reduced bacterial counts of vegetations compared with daptomycin alone but was significantly less effective than vancomycin plus gentamicin. The efficacy of daptomycin-gentamicin did not differ significantly from that of penicillin G procaine-gentamicin. The lack of enterococcal killing by daptomycin alone in serum and in experimental endocarditis is probably related to the high protein binding of the agent.
Antiseptic and antibiotic resistance plasmid in Staphylococcus aureus that possesses ability to confer chlorhexidine and acrinol resistance
Authors: Yamamoto T , Tamura Y , Yokota T
Published: June 2012

Plasmid pSAJ1 from a methicillin- and gentamicin-resistant strain of Staphylococcus aureus had am molecular size of 50 kilobases and conferred resistance not only to kanamycin, gentamicin, tobramycin, amikacin, benzalkonium chloride, acriflavin, and ethidium bromide but also to chlorhexidine. In addition, the cloned antiseptic resistance gene(s) manifested acrinol resistance in Escherichia coli.
No cytogenetic effects of quinolone treatment in humans
Authors: Mitelman F , Kolnig A M , Strömbeck B , Norrby R , Kromann-Andersen B , Sommer P , Wadstein J
Published: June 2012

Cytogenetic effects of ciprofloxacin (500 to 2,000 mg daily) and ofloxacin (200 mg daily) were studied in lymphocytes from 31 patients treated for 1 to 10 weeks. Blood samples for cytogenetic analysis were taken before the start of treatment from all patients, after 1 week from 25 patients, and after 2, 4, 6, and 10 weeks from six patients. No chromosome-damaging effect could be demonstrated in any treatment group. The mean aberration yields for each cytogenetic parameter studied and the total number of aberrations were all normal at each sampling occasion.
Iontophoretic application of tobramycin to uninfected and Pseudomonas aeruginosa-infected rabbit corneas
Authors: Hobden J A , Rootman D S , O'Callaghan R J , Hill J M
Published: June 2012

Pseudomonas aeruginosa keratitis was induced in rabbits to study the effects of corneal infection on the delivery of tobramycin by iontophoresis. Some rabbits were treated by use of an eye cup with no current as a control for iontophoresis, and others were treated with fortified drops (1.36%) delivered topically for comparison with results of earlier studies. One hour after treatment with tobramycin, the concentration of drug in the infected corneas was compared with that achieved in mock-infected and uninfected eyes. Iontophoresis of 25 mg of tobramycin per ml at 0.8 mA for 10 min delivered significantly more drug (P = 0.0001) to corneal tissue than did drops or use of an eye cup without current in P. aeruginosa-infected eyes mock-infected eyes, or uninfected eyes. Tobramycin concentrations in the infected corneas (605.9 micrograms/g) were not significantly different (P = 0.815) from the concentrations in mock-infected eyes (641.4 micrograms/g), but were lower (P = 0.007) than those obtained by iontophoresis in uninfected corneas (853.6 micrograms/g). Use of an eye cup without current delivered tobramycin equally to infected, mock-infected, and normal eyes, i.e., 176.5, 171.0, and 163.1 micrograms/g, respectively (P greater than 0.709). Tobramycin delivered by use of fortified drops delivered topically was detectable in mock-infected corneas (20 micrograms/g) and P. aeruginosa-infected corneas (6.0 micrograms/g). These results suggest that iontophoresis has value as an ocular drug delivery system and that an eye cup could also be useful in a therapeutic regimen for ocular infections.
In vitro susceptibilities of Ehrlichia risticii to eight antibiotics
Authors: Rikihisa Y , Jiang B M
Published: June 2012

Inhibition of the proliferation of Ehrlichia risticii cultured in murine macrophage P388D1 cells by eight antibiotics was evaluated by indirect fluorescent-antibody staining with an antiserum specific to E. risticii. There was a negative correlation between the percentage of infected cells and the log10 of the concentrations of all antibiotics examined. The ranks of the antibiotics in the order of 50% inhibitory concentrations (on a microgram-per-milliliter basis) after 48 h of exposure were as follows: demeclocycline, doxycycline, and oxytetracycline less than minocycline less than rifampin less than tetracycline less than erythromycin and nalidixic acid. When the antibiotics were removed after 48 h of incubation, continuous inhibition of proliferation was evident at 72 h. At 96 h regrowth of the organisms occurred in most of the cultures. The rate of regrowth was the highest with nalidixic acid, followed by erythromycin, at all concentrations of the antibiotic tested. Regrowth was observed with less than 0.1 microgram of minocycline per ml and less than 0.01 microgram of oxytetracycline, tetracycline, and doxycycline per ml. With more than 0.01 microgram of demeclocycline per ml, however, the inhibition persisted for up to 72 h after removal of the antibiotic. These results indicate that demeclocycline was slightly more effective than doxycycline, oxytetracycline, and minocycline in eliminating E. risticii in macrophages in vitro, whereas tetracycline and rifampin were less effective. Nalidixic acid and erythromycin were ineffective.
Comparative activities of cefuroxime, amoxicillin-clavulanic acid, ciprofloxacin, enoxacin, and ofloxacin against aerobic and anaerobic bacteria isolated from bite wounds
Authors: Goldstein E J , Citron D M
Published: June 2012

We studied the comparative in vitro activities of 10 oral antimicrobial agents against 147 aerobic and 61 anaerobic bacteria making up species in 13 genera (Staphylococcus aureus, streptococci, Eikenella corrodens, Pasteurella multocida, Haemophilus-Actinobacillus spp., M-5, EF-4, Moraxella spp., Flavobacterium IIb, Bacteroides melaninogenicus, Bacteroides spp., Fusobacterium spp., and Peptostreptococcus spp.) that were isolated from bite wounds. Cefuroxime was generally greater than fourfold more active than cephalexin and cefadroxil against all aerobic isolates, including Pasteurella multocida. The fluoroquinolones were highly active against most aerobic isolates but were less active against anaerobic isolates. Ciprofloxacin was generally more active than either enoxacin or ofloxacin. Discrepancies of greater than 30% in the interpretation of susceptibilities between break points suggested by the National Committee for Clinical Laboratory Standards and those related to oral dose peak levels (one-half to one-quarter of maximum achievable concentrations) were noted in 14% (18 of 130) of the instances.
Activities of amikacin, roxithromycin, and azithromycin alone or in combination with tumor necrosis factor against Mycobacterium avium complex
Authors: Bermudez L E , Young L S
Published: June 2012

The effect of amikacin and two new macrolides (roxithromycin and azithromycin) used either alone or in combination with recombinant tumor necrosis factor (TNF) to inhibit or kill Mycobacterium avium complex in human macrophages was examined in vitro. Macrophage monolayers infected with M. avium complex (strain 101, serotype 1) were treated with antibiotics or TNF by using three different protocols: (i) antibiotics or TNF was added to the monolayers immediately after infection and washed out after 24 h, (ii) antibiotics or TNF was replenished daily for 4 dys, or (iii) infected macrophage monolayers were treated with antibiotics plus TNF for 4 consecutive days. The number of viable intracellular bacteria was determined after 2 and 4 days of treatment by lysing cultured macrophages. Treatment for 24 h resulted in an inhibition of growth, as determined by macrophage lysis at day 4, for all three antimicrobial drugs and killing of 22% of intracellular bacteria after treatment with TNF. After treating the monolayers with amikacin, roxithromycin, or azithromycin for 4 consecutive days and replenishing the drug concentration daily, we observed 18 +/- 6, 20 +/- 4, and 22 +/- 1% killing, respectively. TNF (100 U/ml) was added daily to the monolayers, which resulted in 54 +/- 5% killing after 4 days. Combinations of antibiotics with TNF were associated with 62 +/- 3% killing with TNF-azithromycin, 73 +/- 6% killing with TNF-roxithromycin, and 56 +/- 4% killing of intracellular M. avium complex with TNF-amikacin after 4 days. The mycobactericidal effect was enhanced (91 +/- 4% killing by roxithromycinamikacin). Combinations of antimicrobial agents with immunomodulators like TNF may be useful for treatment of M. avium complex infection.
Genetic analysis of gentamicin resistance in methicillin- and gentamicin-resistant strains of Staphylococcus aureus isolated in Dublin hospitals
Authors: Storrs M J , Courvalin P , Foster T J
Published: June 2012

Methicillin- and gentamicin-resistant strains of Staphylococcus aureus isolated in Dublin hospitals have been classified into groups I, II, and III based on resistance to antimicrobial agents and plasmid profiles. Each group expresses a characteristic level of resistance to gentamicin, tobramycin, and sisomicin. Enzyme assays showed that resistant strains expressed 2"-aminoglycoside phosphotransferase-6'-aminoglycoside transferase activity by a determinant which is known to be chromosomally located. The gentamicin resistance (Gmr) determinants were transferred from group I, II, or III strains by transduction into a laboratory strain where each expressed the same low level of resistance. This finding suggests that high-level resistance in some clinical strains is due to a second, unlinked resistance mechanism. No evidence was obtained by hybridization experiments that clinical isolates or spontaneous mutants expressing high-level Gmr carried more than one copy of the Gmr determinant, thus eliminating the possibility that a gene dosage effect was responsible for high-level resistance. Hybridization experiments with transductants and wild strains suggested that the Gmr determinant was located at homologous sites in wild strains from different groups, although restriction site differences were observed in flanking sequences. Electron microscope analysis of a cloned Gmr determinant and genetic evidence suggested that a Dublin clinical isolate harbored a transposon very similar to Tn4001.
Activity of fluoroquinolone antibiotics against Plasmodium falciparum in vitro
Authors: Divo A A , Sartorelli A C , Patton C L , Bia F J
Published: June 2012

The fluoroquinolone antibiotics are structurally related to nalidixic acid. Their primary antibacterial action appears to be mainly due to inhibition of DNA gyrase (DNA topoisomerase II). We determined the activity of several fluoroquinolones in vitro against two strains of Plasmodium falciparum, FCC1 (chloroquine susceptible) and VNS (chloroquine resistant). [3H]hypoxanthine incorporation by malarial parasites was determined at 48 and 96 h. The molarity at which each agent caused a 50% decrease in the incorporation of [3H]hypoxanthine compared with that of drug-free controls was defined as the 50% inhibitory concentration. The fluoroquinolones evaluated were amifloxacin, ciprofloxacin, enoxacin, norfloxacin, ofloxacin, and pefloxacin. Other DNA gyrase inhibitors tested were nalidixic acid, oxolinic acid, novobiocin, and coumermycin A1. Among the fluoroquinolones, ciprofloxacin had the lowest 50% inhibitory concentrations at 48 h against both chloroquine-susceptible and -resistant strains of P. falciparum, (0.26 +/- 0.08) x 10(-4) and (0.38 +/- 0.15) x 10(-4) M, respectively (mean +/- standard deviation). Enoxacin had the lowest 50% inhibitory concentrations against FCC1 and VNS at 96 h, 0.23 x 10(-5) and (0.06 +/- 0.04) x 10(-5) M, respectively. With the VNS strain, fractional inhibitory concentration indexes for the combination of ciprofloxacin and tetracycline were calculated at 48 and 96 h to be 0.93 and 0.79, respectively, indicating modest additive effects. The combination of novobiocin with ciprofloxacin showed indifference in the same system. The antimalarial effects of some fluoroquinolones occur at achievable serum concentrations. Whether inhibition of DNA gyrase contributes to the antimalarial activity of the fluoroquinolones is unknown at present.
Endogenous active efflux of norfloxacin in susceptible Escherichia coli
Authors: Cohen S P , Hooper D C , Wolfson J S , Souza K S , McMurry L M , Levy S B
Published: June 2012

Escherichia coli was shown to have an energy-dependent reduced uptake of the fluoroquinolone antimicrobial agent norfloxacin. Studies of everted inner membrane vesicles suggested that this reduced accumulation involved a carrier-mediated norfloxacin active efflux generated by proton motive force with an apparent Km of 0.2 mM and a Vmax of 3 nmol min-1 mg of protein-1. Other hydrophilic, but not hydrophobic, quinolones competed with norfloxacin for transport. Porin (OmpF)-deficient E. coli cells were twofold less susceptible to norfloxacin and showed twice as much energy-dependent reduction in drug uptake. However, active efflux assayed in everted vesicles from the OmpF strain was unchanged compared with that in the parental strain. These findings suggest that in the OmpF mutant decreased outer membrane permeability, combined with active efflux across the inner membrane, in some manner results in decreased steady-state uptake of norfloxacin and lowered drug susceptibility.
Monitoring beta-lactamase activity in vivo by 13C nuclear magnetic resonance spectroscopy
Authors: Mobashery S , Lerner S A , Johnston M
Published: June 2012

A 13C-labeled cephalothin, 7 beta-(2-thienylacetamido)-3-[acetoxy-13C1]methyl-3-cephem-4- carboxylate (compound 1), has been prepared and used to monitor beta-lactamase activities by 13C nuclear magnetic resonance spectroscopy. Time-elapsed spectral analysis of the reaction of the labeled cephalothin with the TEM-2 beta-lactamase purified from Escherichia coli revealed the progressive loss of the cephalothin acetyl resonance at 176.8 ppm and accumulation of an acetate signal at 184.3 ppm. Spectral results identical to those observed in the in vitro experiment were obtained when compound 1 was incubated with cell suspensions of E. coli JSR-O (pBR322), which contains the plasmid-encoded TEM-2 beta-lactamase, and Enterobacter cloacae strains that contain a class I chromosomal beta-lactamase. Pseudo-first-order rate constants for the lactamase-catalyzed formation of acetate from cephalothin in vivo were obtained by integration of the 13C-acetyl resonances of compound 1 during timed incubations with cell preparations. These results constitute the first demonstration of the ability to monitor beta-lactamase activity in viable cells by nuclear magnetic resonance spectroscopy.
Mechanism of action of DuP 721: inhibition of an early event during initiation of protein synthesis
Authors: Eustice D C , Feldman P A , Zajac I , Slee A M
Published: June 2012

The mode of action of DuP 721 was investigated. This compound was active primarily against gram-positive bacteria, including multiply resistant strains of staphylococci. Although inactive against wild-type Escherichia coli, DuP 721 did inhibit E. coli when the outer membrane was perturbed by genetic or chemical means. Pulse-labeling studies with E. coli PLB-3252, a membrane-defective strain, showed that DuP 721 inhibited amino acid incorporation into proteins. The 50% inhibitory concentration of DuP 721 for protein synthesis was 3.8 micrograms/ml, but it was greater than 64 micrograms/ml for RNA and DNA syntheses. The direct addition of DuP 721 to cell-free systems did not inhibit any of the reactions of protein synthesis from chain initiation through chain elongation with either synthetic or natural mRNA as template. However, cell extracts prepared from DuP 721 growth-arrested cells were defective in initiation-dependent polypeptide synthesis directed by MS2 bacteriophage RNA. These cell-free extracts were not defective in polypeptide elongation or in fMet-tRNA(fMet)-dependent polypeptide synthesis stimulated by poly(G.U). We conclude, therefore, that DuP 721 exerts its primary action at a step preceding the interaction of fMet-tRNA(fMet) and 30S ribosomal subunits with the initiator codon.