bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative in vitro activity of semisynthetic penicillins against Proteeae
Authors: Hawkey P M , Pedler S J , Turner A
Published: June 2012

The in vitro susceptibilities of 181 isolates of precisely identified Proteeae species to five semisynthetic penicillins were determined with low and high inocula. Significant differences in susceptibility patterns among various Proteeae species to the penicillins examined were demonstrated. Providencia stuartii was clearly distinguished from Providencia alcalifaciens by its greater resistance to the antibiotics tested.
Intrathecal penetration of N-formimidoyl thienamycin in normal rabbits: potentiation by coadministration of renal dipeptidase enzyme inhibitor
Authors: Chow A W , Finlay K R , Stiver H G , Carlson C L
Published: June 2012

The intrathecal penetration of N-formimidoyl thienamycin (MK0787) with or without coadministration of the renal dipeptidase enzyme inhibitor (MK791) in normal rabbits was studied immediately before and after the third dose of 40 mg/kg infused intravenously at daily 6-h intervals. Mean +/- standard error peak concentrations in cerebrospinal fluid were 0.23 +/- 0.02 and 0.53 +/- 0.12 micrograms/ml without and with coadministration of MK791, respectively (P less than 0.05, Student's t test). Penetration into cerebrospinal fluid (based on the ratio of cerebrospinal fluid to plasma area under the concentration-time curves) were 4.4 and 6.0%, respectively. N-Formimidoyl thienamycin penetrated uninflamed meninges, and peak concentrations were significantly augmented by coadministration of MK791.
Antifungal activity in human urine and serum after ingestion of garlic (Allium sativum)
Authors: Caporaso N , Smith S M , Eng R H
Published: June 2012

A fresh extract of garlic (Allium sativum) was administered orally to human volunteers. At intervals, serum and urine were collected and assayed for antifungal activity. The maximum tolerable dose was determined to be 25 ml of garlic extract. Larger amounts caused severe burning sensations in the esophagus and the stomach and vomiting. After oral ingestion of 25 ml of the extract, anticandidal and anticryptococcal activities were detected in undiluted serum 0.5 and 1 h after ingestion. No detectable antifungal activity was found in the excreted urine at any time after oral ingestion. Oral garlic is of limited value in the therapy of human fungal infections.
Antimicrobial Activity of Cefmenoxime Compared with Those of Other Cephalosporins
Authors: Schell Ronald F. , Smith Bruce R. , Lefrock Jack L. , Francisco Maryalice
Published: June 2012

The antimicrobial activity of cefmenoxime was compared with those of cefamandole, cefoperazone, cefotaxime, cephalothin, and moxalactam. In general, the activity of cefmenoxime was equivalent to those of the other cephalosporins. Cefmenoxime appears to be a potent antimicrobial agent against most gram-negative microorganisms other than
Pseudomonas aeruginosa
and
Acinetobacter
spp.
Activity of 1-(2'-fluoro-2'-deoxy-beta-D-arabinofuranosyl)thymine against herpes simplex virus in cell cultures and rabbit eyes
Authors: Trousdale M D , Nesburn A B , Su T L , Lopez C , Watanabe K A , Fox J J
Published: June 2012

A new antiviral compound 1-(2'-fluoro-2'-deoxy-beta-D-arabinofuranosyl)thymine (2'-fluoro-5-methyl-ara-uracil [FMAU]), was compared with acyclovir and idoxuridine in vitro against two strains of both herpes simplex virus type 1 (HSV-1) and HSV-2. Determinations of the 50% effective dose varied slightly with each strain and with the host cells employed. The 50% effective dose for FMAU and acyclovir against HSV-1 ranged from 0.1 microM to 0.5 to 0.6 microM in rabbit kidney cells and from 0.5 microM to 0.6 to 0.78 microM in Vero cells. Beginning 4 days post-inoculation, topical FMAU therapy given five times per day to rabbits with acute herpetic keratitis either suppressed or delayed the severity of corneal epithelial involvement, conjunctivitis, iritis, and corneal clouding. Responses to treatment with FMAU were similar to those obtained with acyclovir and significantly better than those attained with idoxuridine and vidarabine. At 30 to 40 days after the end of treatment, rabbit eyes were subjected to iontophoresis with epinephrine in an attempt to induce reactivation and enhance detection of previously latent HSV-1. Latent HSV-1 was detected in 67 to 92% of trigeminal ganglia in FMAU-treated animals and in 90% of placebo-treated animals.
Single-dose cefonicid therapy for urinary tract infections
Authors: Pontzer R E , Krieger R E , Boscia J A , McNamee W , Levison M E , Kaye D
Published: June 2012

The efficacy of single-dose therapy with cefonicid (1 g intramuscularly) and multidose therapy with amoxicillin (500 mg orally three times a day for 7 days) was compared for the treatment of uncomplicated lower urinary tract infection in women. Of 50 patients with symptoms of lower urinary tract infection randomized to receive either cefonicid or amoxicillin, 39 were infected with greater than or equal to 10(5) bacteria per ml. At early posttherapy follow-up (5 to 18 days), 19 of 21 (90%) cefonicid-treated patients and 16 of 18 (89%) amoxicillin-treated patients were cured. At late posttherapy follow-up (6 to 7 weeks), 16 of 18 (89%) cefonicid-treated patients and 14 of 15 (93%) amoxicillin-treated patients were cured. One patient was lost to follow-up in each late follow-up group. There were fewer side effects in the cefonicid-treated group. There were significantly more organisms resistant to amoxicillin than to cefonicid in the study population. Considering the small size of the series, single-dose therapy with cefonicid for lower urinary tract infection in women appears to be as safe and effective as conventional multidose therapy with amoxicillin.
Analysis of plasmids in nosocomial strains of multiple-antibiotic-resistant Staphylococcus aureus
Authors: Lyon B R , May J W , Skurray R A
Published: June 2012

Nosocomial infections caused by Staphylococcus aureus strains resistant to methicillin and multiple antibiotics have reached epidemic proportions in Melbourne, Australia, over the past 5 years. Plasmid analysis of representative clinical isolates demonstrated the presence of three classes of plasmid DNA in most strains. Resistance to gentamicin, kanamycin, and tobramycin was usually mediated by an 18-megadalton plasmid but could also be encoded by a related 22-megadalton plasmid. Two distinguishable plasmids of 3 megadaltons each endowed resistance to chloramphenicol, and the third class consisted of small plasmids, each approximately 1 megadalton in size, with no attributable function. An extensive array of resistance determinants, including some which have usually been associated with a plasmid locus, were found to exist on the chromosome. Evidence that resistance to gentamicin, kanamycin, and tobramycin is chromosomally encoded in some clinical isolates suggests that this determinant may have undergone genetic translocation onto the staphylococcal chromosome.
Increase of amikacin half-life during therapy in patients with renal insufficiency
Authors: Blaser J , Rüttimann S , Bhend H , Lüthy R
Published: June 2012

Serum kinetics of amikacin were investigated in 17 severely ill patients. During both the first and last dose intervals of therapy, the serum concentration time course of every patient was documented by 17 blood samples. Six of the patients had moderate to severe renal insufficiency (serum creatinine greater than 1.5 mg/100 ml). In this group of patients, a pronounced rise in serum half-life of amikacin was observed, increasing from a mean of 11.2 to 21.5 h for the first and last interval, respectively. In contrast, mean half-life remained stable in the group of 11 patients with normal renal function. No change in mean serum creatinine occurred in either group, when data from the beginning and the end of therapy were compared. Therefore, the increase of amikacin half-life is apparently not due to a reduction of the glomerular filtration rate, but rather to a decrease of the ratio of amikacin to creatinine clearance. Indeed, a significant reduction of this ratio could be shown in the seven patients in which 24-h creatinine clearance was determined during the first and last day of therapy. This phenomenon is discussed in the context of aminoglycoside accumulation in deep compartments. We conclude that the daily dose of amikacin has to be reduced during therapy in patients with impaired, but stable, renal function.
Synergy of combinations of vancomycin, gentamicin, and rifampin against methicillin-resistant, coagulase-negative staphylococci
Authors: Lowy F D , Chang D S , Lash P R
Published: June 2012

The activity of combinations of vancomycin (2 or 10 micrograms/ml), gentamicin (0.3 micrograms/ml), and rifampin (0.03 micrograms/ml) against methicillin-resistant, coagulase-negative staphylococcal isolates was determined by the time-kill method. Combinations of rifampin with gentamicin or with vancomycin 2 micrograms/ml demonstrated enhanced killing against 13 of 17 and 13 of 25 strains, respectively. However, rifampin-resistant strains were selected with the latter combination in the remaining 12 of 25 studies.
In vitro susceptibility of Mycobacterium fortuitum to amoxicillin or cephalothin in combination with clavulanic acid
Authors: Cynamon M H , Palmer G S
Published: June 2012

The comparative in vitro activity of cefoxitin, cephalothin, amoxicillin, and clavulanic acid in combination with the latter two agents against 13 isolates of Mycobacterium fortuitum was evaluated by agar dilution susceptibility testing. Amoxicillin was more active than cephalothin but less active than cefoxitin against the strains tested. Clavulanic acid in combination with these beta-lactams usually improved the activity by one or two dilutions compared with the beta-lactams alone.
Bactericidal activities of new beta-lactam antibiotics against Bacteroides fragilis
Authors: Yu P K , Washington J A
Published: June 2012

The bactericidal activities of cefoxitin, cefoperazone, cefotaxime, moxalactam, mezlocillin, and piperacillin were determined in duplicate against low and high inocula of each of 10 Bacteroides fragilis strains. Antibiotic concentrations resulting in 99.9% killing were established by quantitation of the inocula just before anaerobic incubation of tests and by subcultures of volumes sufficient to accurately determine less than or equal to 0.1% survivors. Inoculum effects on inhibitory and bactericidal activities were least for cefoxitin and greatest for cefoperazone and cefotaxime. Bactericidal-to-inhibitory concentration ratios of greater than or equal to 8 occurred most frequently with mezlocillin and piperacillin, regardless of inoculum size; however, 55% of the strains tested at the low inoculum size and 38% of those tested at the high inoculum size against the six antibiotics had bactericidal-to-inhibitory concentration ratios of greater than or equal to 4.
Penetration of ceftazidime into cerebrospinal fluid of patients with bacterial meningitis
Authors: Modai J , Vittecoq D , Decazes J M , Wolff M , Meulemans A
Published: June 2012

Four 2-g doses of ceftazidime were infused intravenously over 30 min at 8-h intervals, first between days 2 and 4 and again between days 11 and 20, in 11 patients with bacterial meningitis undergoing treatment with other antibiotics. Concentrations of ceftazidime in serum and cerebrospinal fluid samples obtained 120 or 180 min after dose 4 were measured by high-pressure liquid chromatography. Concentrations in cerebrospinal fluid ranged from 2 to 30 micrograms/ml, depending on the sampling time and the time elapsed since the onset of the disease.
Effect of discontinuous acyclovir treatment on in vitro reactivation of herpes simplex virus from latently infected trigeminal ganglia
Authors: Klein R J , Friedman-Kien A E , DeStefano E
Published: June 2012

Exposing explant cultures of latently infected mouse trigeminal ganglia alternately to acyclovir-containing and drug-free medium led to a significant decrease in the proportion of ganglia containing reactivatable herpes simplex virus. The loss of virus from the explant cultures was not caused by thermal inactivation during prolonged incubation periods. The efficiency of virus elimination may depend on the frequency and duration of the alternating treatment and on the number of latently infected neurons in the ganglia.
Peritoneal absorption of moxalactam
Authors: Stephens N M , Kronfol N O , Kline B J , Polk R E
Published: June 2012

We evaluated the rate and extent of the systemic absorption of moxalactam given intraperitoneally to patients with peritonitis and end-stage renal disease who were being maintained on continuous ambulatory peritoneal dialysis. Moxalactam was administered at a concentration of 200 mg per 2-liter dialysate for the first dose, followed by 60 mg per 2-liter exchange for 23 1-h exchanges. Moxalactam concentrations in serum (mean +/- standard deviation) were 2.5 +/- 0.9 mg/liter after the first hourly dialysis, increasing to 10.3 +/- 4.8 mg/liter after 24 h of drug administration. Moxalactam levels in serum at 1 h were above the minimal inhibitory concentrations for most gram-negative organisms except Pseudomonas aeruginosa. No adverse effects of the drug were observed.
Influence of clindamycin on derepression of beta-lactamases in Enterobacter spp. and Pseudomonas aeruginosa
Authors: Sanders C C , Sanders W E , Goering R V
Published: June 2012

Previous studies in this and other laboratories have shown that derepression of beta-lactamases in strains of Enterobacter and Pseudomonas spp. is responsible for the rapid development of resistance to a variety of beta-lactam antibiotics. The purpose of the current study was to evaluate the effects of clindamycin on derepression of beta-lactamases in these two genera. In tests with four strains of each genus, clindamycin diminished derepression in one isolate of each genus and completely prevented derepression in a second Enterobacter isolate (strain 55). Additional tests with strain 55 revealed that other inhibitors of macromolecular synthesis did not completely prevent derepression of beta-lactamase when tested at concentrations that did not inhibit replication. However, clindamycin did not affect synthesis of beta-lactamase that was constitutively produced in a mutant of this strain (55M). It also did not inhibit derepression of beta-galactosidase in either strain 55 or 55M. Clindamycin did not diminish the bactericidal effects of beta-lactam antibiotics against Enterobacter or Pseudomonas spp. However, it enhanced the bactericidal activity of cefamandole against strain 55. These in vitro effects of clindamycin on strain 55 that were related to prevention of derepression of beta-lactamase were confirmed in vivo with an animal model of infection. These results indicate that in some strains, clindamycin can specifically prevent derepression of beta-lactamases without inhibiting growth. Such a selective effect may provide a new approach for the enhancement of the antibacterial activity of certain beta-lactam antibiotics.
Self-transmissible plasmids in staphylococci that encode resistance to aminoglycosides
Authors: Archer G L , Johnston J L
Published: June 2012

High-level resistance to gentamicin, tobramycin, and kanamycin was transferred between staphylococci of the same and different species by filter mating. Resistance and transfer proficiency were mediated by plasmids ranging from 38 to 54 kilobases in size. All of the plasmids encoded intermediate resistance to amikacin and netilmicin and resistance to ethidium bromide; some encoded beta-lactamase production. None of these plasmids carried resistance to other antibiotics or heavy metals. Transfer of antibiotic resistance occurred by a mechanism similar to that of conjugation, because it was DNase resistant, required cell-to-cell contact, and did not appear to involve phage. The participation of phage in transfer appeared to be unlikely because mijtomicin C-induced lysates of donor isolates did not mediate transfer, filter mating transfer proceeded at high frequency between nonlysogenic donor and recipient cells, and transfer of the aminoglycoside resistance plasmid mobilized the transfer of as many as five additional plasmids. All 17 gentamicin-resistant Staphylococcus aureus and all 6 Staphylococcus epidermidis isolates obtained from an outbreak of staphylococcal infections in a newborn nursery contained conjugative plasmids, as did all 6 gentamicin-resistant S. aureus isolates from bacteremic adults. However, only 3 of 10 gentamicin-resistant S. epidermidis isolates from colonized cardiac surgery patients and 1 of 2 S. epidermidis isolates from patients with prosthetic valve endocarditis transferred gentamicin resistance by filter mating. The recent increase in nosocomial infections caused by gentamicin-resistant staphylococci may be partially explained by the evolution of self-transmissible plasmids in these isolates.
In vitro and in vivo antibacterial activity of AT-2266
Authors: Kouno K , Inoue M , Mitsuhashi S
Published: June 2012

AT-2266 [1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3-carbo xylic acid] showed a broad spectrum of antibacterial activity against gram-positive and gram-negative microorganisms, including Pseudomonas aeruginosa. The in vitro antibacterial activity of AT-2266 was in general comparable to that of norfloxacin, but much higher than that of pipemidic or nalidixic acid. The 90% minimal inhibitory concentrations (MIC90s) of AT-2266 for P. aeruginosa resistant to gentamicin (MIC range, 25 to greater than 200 microgram/ml) and Enterobacteriaceae resistant to nalidixic acid (25 to greater than 1,600 micrograms/ml) were 3.13 and 12.5 micrograms/ml, respectively. The to nalidixic acid (25 to 1,600 micrograms/ml) were 3.13 and 12.5 micrograms/ml, respectively. The MICs of AT-2266 were only slightly affected by the addition of horse serum or sodium cholate, by the pH of the medium, and by inoculum size. AT-2266 was sodium cholate, by the pH of the medium, and by inoculum size. AT-2266 was bactericidal at concentrations near its MIC value. The 50% effective doses of AT-2266 after oral administration against systemic infections in mice were about 1/2 those of norfloxacin, about 1/10 those of pipemidic acid, and between 1/20 and 1/40 those of nalidixic acid.
Comparative metabolism of chloramphenicol in germfree and conventional rats
Authors: Wal J M , Corpet D E , Peleran J C , Bories G F
Published: June 2012

The action of gut microflora on the metabolism of chloramphenicol (CP) was studied in germfree (GF) and conventional (CV) rats after administration of single oral doses of tritiated CP. There were similarities in the metabolic pathways of CP in the GF and CV animals, i.e., rapid absorption, hepatic glucuroconjugation, and biliary excretion of the CP conjugate. CP, CP-oxamic acid, CP-alcohol, and CP-base were present in similar proportions in the urine of both GF and CV rats. Differences observed included the slow elimination of total radioactivity and a reduced proportion of the urinary excretion versus the fecal excretion in the GF Reduction products which were present in much greater quantities in the urine and feces of CV rats are compatible with the generally described hydrolysis of the CP-glucuronide, followed by a nitroreduction of the CP by the gut microflora and the reabsorption of a part of the products formed. In GF rats, CP-glucuronide was the major fecal metabolite, a portion of it having been reabsorbed and excreted in the urine. Although in lesser amounts, reduction products were still present as urinary metabolites in GF rats. Such a reduction in the tissues might produce active intermediate that could be related to CP toxicity.
Multiple-dose pharmacokinetics of ceftazidime in cancer patients
Authors: Garcia I , Fainstein V , Smith R G , Bodey G P
Published: June 2012

The pharmacokinetic parameters of ceftazidime were determined in 25 patients with neoplastic diseases. A group of 13 patients each received 1 g of ceftazidime over 15 min as a single intravenous dose. The mean peak drug concentration in serum was 77.4 micrograms/ml, and the serum half-life was 144 min. Urinary excretion at 12 h was 64.5%. These 13 patients also received 2 g of ceftazidime over 15 min at 8-h intervals for 7 or 8 days. The mean peak drug concentrations in serum were 103.6 micrograms/ml on day 1 and 87 micrograms/ml on day 7 or 8. A second group of 12 patients received 1 g of ceftazidime over 30 min, followed by 1 g over 2 h and every 4 h thereafter. The mean peak drug concentration in serum at 30 min was 57.5 micrograms/ml. Average peak and trough levels obtained on day 2 or 3 were 65 and 34.8 micrograms/ml, respectively, and remained in this range thereafter. The above-mentioned dose schedules produced high and adequate ceftazidime concentrations in serum.
Transfer of plasmids from Escherichia coli to Pseudomonas aeruginosa: characterization of a Pseudomonas aeruginosa mutant with enhanced recipient ability for enterobacterial plasmids
Authors: Tardif G , Grant R B
Published: June 2012

Pseudomonas aeruginosa strain GT424, derived by the transfer of plasmid R45 to strain GT1, was shown to have an Era+ phenotype (enhanced recipient ability) for enterobacterial plasmids from incompatibility (Inc) groups C, FI, FII, J, N, W, and X. Increase in transfer frequency ranged from 10 to 10(6)-fold. Plasmids of IncFII, IncJ, and IncX were found to be transmissible only to the Era+ strain. Plasmids of Inc groups A-C, M, and T transferred at low frequency (less than 10(-7)) to both GT1 and GT424 and did not respond to the Era+ character of the latter. Also not responsive to the Era character were plasmids R144drd3 (IncI alpha) and RP1 (IncP), which transferred to both GT424 and GT1 at intermediate (10(-4)) and high frequencies (10(-1)), respectively. All plasmid-mediated antibiotic resistances that could be measured as well as UV resistance and susceptibility were found to be expressed in P. aeruginosa. Plasmid-coded phage susceptibilities, however, generally were not phenotypically manifested in the P. aeruginosa strains. The physical structure of plasmids in P. aeruginosa could be classified into four major types. Some of the plasmids underwent additions or deletions and were unstable; the majority, however, appeared to integrate into the chromosome. Some members of IncN, IncC, IncJ, and IncP were found to be transmissible from P. aeruginosa back to Escherichia coli. This is the first report of the successful transfer to P. aeruginosa of plasmids from many of the Inc groups that have been defined in Enterobacteriaceae, namely, FI, I alpha, J, M, T, and X.
Evaluation of an automated fluorescence polarization immunoassay for vancomycin
Authors: Filburn B H , Shull V H , Tempera Y M , Dick J D
Published: June 2012

An automated fluorescence polarization immunoassay for the determination of vancomycin levels in serum was evaluated. The vancomycin assay is a homogeneous competitive inhibition immunoassay based on changes in fluorescence polarization that occur with antibody binding. This assay was compared with a liquid chromatographic assay and an agar well diffusion bioassay method by using clinical serum specimens and controls. Linear regression analysis of the data obtained on clinical specimens by the three methods resulted in correlation coefficients of 0.97 for the fluorescence polarization immunoassay versus the liquid chromatographic assay (n = 60), 0.90 for the fluorescence polarization immunoassay versus the bioassay (n = 57), and 0.90 for the liquid chromatographic assay versus the bioassay (n = 57). Repetitive analysis of control sera containing 7, 35, and 75 micrograms of vancomycin per ml by the fluorescence polarization immunoassay yielded coefficients of variation of 3.0, 1.7, and 2.3, respectively. No interference was demonstrated in spiked hemolytic, lipemic, or icteric sera, and the assay was free of matrix effects. The automated fluorescence polarization immunoassay system offers a rapid, efficient, and accurate method for monitoring vancomycin serum levels for both toxicity and efficacy.
Activity of purine analogs against Leishmania tropica within human macrophages in vitro
Authors: Berman J D , Lee L S , Robins R K , Revankar G R
Published: June 2012

The activity of purine analogs against Leishmania tropica in human monocyte-derived macrophages in vitro was determined. Formycin B, formycin A, formycin B and A monophosphate, and formycin A triphosphate all had 50% effective doses of 0.02 to 0.04 microM and eliminated 90% of organisms at less than or equal to 0.5 microM. Allopurinol ribonucleoside was much less active: the 50% effective dose was 76 to 190 microM, and 90% of organisms were not eliminated at the highest dose tested (190 microM). 7-Deazainosine had a low 50% effective dose (0.2 microM), but only 80% of organisms were eliminated at 4 microM. Thio derivatives were as active as or less active than the parent compounds. These data suggest that certain inosine analogs are much more active than others against macrophage-contained Leishmania spp. such as are found in human lesions. However, because toxicity to the human macrophage hosts generally paralleled antileishmanial activity, the more active compounds might also be more toxic to human cells. The activity of 3-deazaguanosine (50% effective dose, 3.6 microM) in this model suggests that guanosine derivatives may have potential as antileishmanial agents.
Pharmacokinetics of ceftizoxime in patients undergoing continuous ambulatory peritoneal dialysis
Authors: Burgess E D , Blair A D
Published: June 2012

The pharmacokinetics of ceftizoxime were studied in 12 patients on continuous ambulatory peritoneal dialysis. After a 3-g intravenous dose, the steady-state volume of distribution was 0.23 +/- 0.05 liter kg-1, with an elimination half-life of 9.7 +/- 5.1 h. The peritoneal clearance of ceftizoxime (2.8 +/- 0.7 ml min-1) contributed modestly to the overall serum clearance of the drug (17.1 +/- 7.4 ml min-1) and was greater than the renal clearance (0.8 +/- 0.8 ml min-1). The peritoneal concentration rose to 91 +/- 29 micrograms ml-1 at 6 h, which was 0.61 +/- 0.17 of the serum concentration. A 3-g intravenous dose of ceftizoxime given every 48 h would result in adequate activity against most susceptible organisms, but more frequent dosing may be necessary for less susceptible organisms.
Penetration of sulbactam and ampicillin into peritoneal fluid
Authors: Wise R , Donovan I A , Andrews J M , Drumm J , Bennett S
Published: June 2012

Twenty-five patients undergoing elective intraabdominal surgery received either 1 or 2 g of ampicillin together with 1 g of sulbactam intravenously before surgery. The peritoneal levels of the agent were measured. Both compounds penetrated peritoneal fluid readily; the mean percentage of penetration by ampicillin was 92%; that of sulbactam was 96%. After 1 g of each agent, the peritoneal levels of sulbactam were 47% greater than those of ampicillin. Our results suggest that 2 g of ampicillin plus 1 g of sulbactam should provide peritoneal levels that would inhibit most susceptible beta-lactamase-producing pathogens encountered in intraabdominal sepsis.
In vitro activities of new beta-lactam antibiotics against Acinetobacter spp
Authors: Garcia I , Fainstein V , LeBlanc B , Bodey G P
Published: June 2012

The in vitro activities of new beta-lactam antibiotics was studied and compared with those of other known agents against 51 clinical isolates of Acinetobacter calcoaceticus subsp. anitratus and 23 isolates of A. calcoaceticus subsp. lwoffi. Of the new beta-lactam antibiotics, imipemide (N-formimidoyl thienamycin), ceftazidime, ceftizoxime, ceftriaxone, and piperacillin demonstrated good activities. The minimal inhibitory concentrations for A. calcoaceticus subsp. lwoffi were lower than those obtained for A. calcoaceticus subsp. anitratus.
Multiple-dose pharmacokinetics of ceftazidime and its influence on fecal flora
Authors: Kemmerich B , Warns H , Lode H , Borner K , Koeppe P , Knothe H
Published: June 2012

Eight healthy volunteers each received 2.0 g of ceftazidime by constant intravenous infusion over 20 min twice daily every 12 h for 8 days. Concentrations of ceftazidime in serum and urine were measured by a microbiological assay and by high-pressure liquid chromatography. Qualitative and quantitative studies on aerobic and anaerobic fecal flora were carried out before, during, and 2 weeks after the end of treatment. The mean (+/- standard deviation) maximum drug concentration in serum at the end of the 20-min infusion (day 1) was 185.5 +/- 28.5 micrograms/ml, decreasing to 0.8 +/- 0.4 microgram/ml after 12 h. The mean recovery of drug in urine at 12 h was 71.5 +/- 12.2%. Pharmacokinetic parameters calculated on the basis of a two-compartment model were as follows: elimination half-life, 110.5 +/- 15.2 min; volume of distribution at steady state, 21.2 +/- 2.6 liters/100 kg; volume of distribution by the area method, 26.2 +/- 4.0 liters/100 kg; area under the serum concentration-time curve, 293.3 +/- 47.8 micrograms X h/ml; total body clearance, 116.4 +/- 20.3 ml/min per 70 kg; renal clearance, 82.2 +/- 15.1 ml/min per 70 kg. The agar diffusion test and high-pressure liquid chromatographic analysis showed a good correlation of results. Metabolites of ceftazidime could not be detected by high-pressure liquid chromatography in serum or urine. No accumulation of ceftazidime could be observed during the 8-day study period. Mean maximum drug levels in serum were 185.5 to 214.5 micrograms/ml, and mean trough levels were 0.8 to 1.1 micrograms/ml (days 1 to 8). No severe side effects were noted. During ceftazidime treatment, anaerobes were left intact, whereas members of the family Enterobacteriaceae could be isolated from stool in only three of eight subjects. Two weeks after discontinuation of the drug, all stool specimens contained ampicillin- and cefazolin-resistant gram-negative rods.
Nucleic acid hybridization for measurement of effects of antiviral compounds on human cytomegalovirus DNA replication
Authors: Gadler H
Published: June 2012

A nucleic acid hybridization technique has been developed to study the effect of different antiviral compounds on the replication of human cytomegalovirus in vitro. One laboratory strain of human cytomegalovirus, Ad. 169, and six clinical isolates were studied. Doses needed for 50% inhibition of viral DNA replication were calculated for foscarnet, acyclovir, and arabinosyladenine. The mean 50% inhibition dose values obtained were 179 microM for foscarnet, 82 microM for acyclovir, and 44 microM for arabinosyladenine. This method yields values that agree with earlier reports, and it offers great advantages over usual methods to date for studying inhibition of viral DNA replication.
Metabolism and pharmacokinetics of aztreonam in healthy subjects
Authors: Swabb E A , Singhvi S M , Leitz M A , Frantz M , Sugerman A
Published: June 2012

The metabolism and pharmacokinetics of aztreonam (SQ 26,776) were studied in four healthy male volunteers, each of whom received single 500-mg intravenous and intramuscular doses of 14C-labeled drug according to a two-way crossover design. Serial samples of serum, urine, and feces were assayed for aztreonam and metabolites. Serum pharmacokinetics of aztreonam administered intravenously were described by an open, linear, two-compartment kinetic model. Kinetics of intramuscular aztreonam followed a one-compartment model with first-order absorption and elimination. Intramuscular bioavailability was 100%. After either intravenous or intramuscular administration, aztreonam was eliminated primarily by urinary excretion of unchanged drug (about 66% of dose), whereas only 1% of the dose was found as unchanged drug in the feces, presumably owing to biliary secretion. The average elimination half-life of aztreonam was 1.6 and 1.7 h, respectively, for intravenous and intramuscular administration. Aztreonam did not undergo extensive metabolism; the most prominent biotransformation product of aztreonam was SQ 26,992, the compound resulting from the hydrolytic opening of the beta-lactam ring. Urinary and fecal SQ 26,992 constituted 7 and 3% of the administered dose, respectively. SQ 26,992 was eliminated at a considerably slower rate than was aztreonam.
In vitro antibacterial activity of concentrated polyethylene glycol 400 solutions
Authors: Chirife J , Herszage L , Joseph A , Bozzini J P , Leardini N , Kohn E S
Published: June 2012

It was found that concentrated polyethylene glycol 400 (PEG 400) solutions have significant antibacterial activity against various pathogenic bacteria, including Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. This effect might be attributed to two effects: lowering of water activity and, superimposed on this, the specific action of PEG-400 molecules on bacterial cells. Phase-contrast microscopic observations of cells placed in contact with PEG 400 revealed clumping and morphological changes of bacterial cells. The larger changes in appearance were evidenced by the species which were more rapidly killed by PEG 400. The results obtained suggested that concentrated PEG 400 solutions may have a potential value in medicine as a topical antibacterial agent. The feasibility of this application is the subject of present investigation.
In vitro activity of midecamycin, a new macrolide antibiotic
Authors: Neu H C
Published: June 2012

Midecamycin, an acetoxy-substituted macrolide antibiotic, was tested against gram-positive and gram-negative bacteria. It inhibited the majority of streptococci, staphylococci, and strains of Haemophilus and Listeria at concentrations of less than 3.1 micrograms/ml. It was less active than erythromycin, and it failed to inhibit erythromycin-resistant isolates.
5-fluorocytosine susceptibility of pathogenic fungi in the presence of allopurinol: potential for improving the therapeutic index of 5-fluorocytosine
Authors: Kerkering T M , Schwartz P M , Espinel-Ingroff A , Turek P J , Diasio R B
Published: June 2012

The minimal inhibitory concentration of 5-fluorocytosine in 18 pathogenic fungal isolates was not altered by either allopurinol (100 microM) or oxypurinol (100 microM). Since allopurinol at this level clinically has been demonstrated to interfere with 5-fluorouracil anabolism, thereby reducing toxicity owing to 5-fluorouracil, allopurinol may be useful in counteracting the 5-fluorouracil-induced myelotoxicity observed in patients being treated with 5-fluorocytosine without interfering with the antifungal activity of 5-fluorocytosine.
Efficacy and selectivity of some nucleoside analogs as anti-human cytomegalovirus agents
Authors: Colacino J M , Lopez C
Published: June 2012

1-(2'-Deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC), 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methyluridine (FMAU), 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouridine (FIAU), and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-ethyluridine (FEAU) were evaluated for antiviral activities against human cytomegalovirus (HCMV) and compared with 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir) and E-5-(2'-bromovinyl)-2'-deoxyuridine (BVDU). The relative anti-HCMV potencies of these compounds, as determined by calculating the dose of drug which inhibited 50% plaque formation, were in order of decreasing potency: FIAC greater than FIAU greater than FMAU greater than acyclovir greater than FEAU greater than BVDU. The antiviral activity of FIAC occurred at levels much lower than those that caused cytotoxic or cytostatic effects in uninfected fibroblasts. Neither thymidine nor deoxycytidine reversed the anti-HCMV activity of FIAC, indicating that this drug was not acting as an analog of the natural nucleosides. FIAC was not phosphorylated by cytosols of HCMV-infected cells to a greater extent that by those of uninfected cells, indicating that, unlike the antiviral activity against herpes simplex virus type 1, the selectivity of this drug is probably not based on a virus-specified pyrimidine kinase.
Antibiotic prophylaxis against streptomycin-resistant and -susceptible Streptococcus faecalis endocarditis in rabbits
Authors: Guze P A , Kalmanson G M , Freedman L R , Ishida K , Guze L B
Published: June 2012

This report describes the capacities of ampicillin, vancomycin, streptomycin, gentamicin, and combinations thereof to prevent endocarditis in rabbits challenged with either streptomycin-resistant (three strains) or streptomycin-susceptible (one strain) Streptococcus faecalis. Vancomycin (15 mg/kg) alone was effective in preventing infection with three of four strains, including two which were streptomycin resistant. Vancomycin (30 mg/kg) alone was effective against the other streptomycin-resistant strain. The vancomycin-gentamicin combination was the only therapeutic regimen to demonstrate complete prophylaxis for all strains regardless of streptomycin susceptibility. The ampicillin-gentamicin combination was variably effective despite in vitro synergism.
Phosphonopeptides as substrates for peptide transport systems and peptidases of Escherichia coli
Authors: Atherton F R , Hall M J , Hassall C H , Lambert R W , Lloyd W J , Lord A V , Ringrose P S , Westmacott D
Published: June 2012

Peptide transport and peptidase susceptibility of the antibacterial agent alafosfalin and other phosphonopeptides have been characterized in Escherichia coli. Phosphonodipeptides were accumulated by a process which appeared to involve multiple permeases; saturation was not achieved even at concentrations of 128 microM. Competition studies showed that these compounds had only a low affinity for the system transporting phosphonooligopeptides and were rapidly taken up by and were inhibitory to E. coli mutants unable to transport the toxic peptide triornithine. Phosphonodipeptides containing D-residues were not appreciably transported. By contrast, phosphonooligopeptides were generally transported by a distinct saturable permease system for which they had a high affinity. This system was identical to that utilized by triornithine. Phosphonooligopeptides with simple monoalkyl substituents at the amino terminus were also transported except in the case of a t-butyl substituent. The oligopeptide permease was also able to transport certain derivatives which contained some residues having D rather than L stereochemistry. Intracellular metabolism of phosphonooligopeptides was initiated almost exclusively by hydrolysis from the N terminus by an L-specific peptidase. This initial hydrolytic activity was unaffected by the aminopeptidase inhibitor bestatin, unlike the final hydrolysis step which yields L-1-aminoethylphosphonic acid from the phosphonodipeptide intermediate.
Effect of piperacillin on tobramycin pharmacokinetics in patients with normal renal function
Authors: Lau A , Lee M , Flascha S , Prasad R , Sharifi R
Published: June 2012

Aminoglycosides are inactivated by extended-spectrum penicillins in vitro and in patients with end-stage renal failure. In this prospective controlled study, we determined the effect of piperacillin on tobramycin pharmacokinetics. In 10 clinically stable male patients with calculated creatinine clearances of greater than or equal to 60 ml/min, serial levels in serum of tobramycin alone and after single 4-g intravenous doses of piperacillin were determined. No statistically significant changes in the concentration of drug in serum, the half-life (t1/2), the elimination rate constant (Ke), the volume of distribution (Vd), or the area under the serum concentration-time curve (AUC0-oo) occurred when tobramycin was used concurrently with piperacillin. Therefore, this antibiotic combination will not result in a clinically significant interaction in patients with normal renal function.
Comparative activities of norfloxacin and fifteen other antipseudomonal agents against gentamicin-susceptible and -resistant Pseudomonas aeruginosa strains
Authors: Forward K R , Harding G K , Gray G J , Urias B A , Ronald A R
Published: June 2012

We compared the activity of norfloxacin (MK-0366), a new orally absorbable derivative of naladixic acid, with those of other antipseudomonal agents against Pseudomonas aeruginosa. Norfloxacin was the most active against both gentamicin-susceptible and gentamicin-resistant strains, having 90% minimal inhibitory concentrations of 2 and 8 micrograms/ml, respectively. This excellent in vitro activity may make norfloxacin effective for oral therapy of P. aeruginosa urinary tract infections.
Trimethoprim and rifampin in combination for chemoprophylaxis of household contacts of patients with invasive infections due to Haemophilus influenzae type b
Authors: Daum R S , Glode M P , Ambrosino D , Halsey N , Goldmann D A , Mather F J , Russell R , Kamon J , Murray M , Band J D
Published: June 2012

We compared the effectiveness of rifampin-trimethoprim in fixed combination (3.75:1) to rifampin alone in the eradication of Haemophilus influenzae type b carriage among contacts of patients with invasive infection caused by this organism. The study population was composed of 127 index patients and 620 contacts. Twenty-six percent of contacts were colonized. Rifampin-trimethoprim eradicated carriage in 77.6% of contacts (71.1% in contacts less than 5 years, 84.2% in contacts greater than or equal to 5 years) whereas rifampin eradicated carriage in 69.9% of contacts (56.4% in contacts less than 5 years, 81.8% in contacts greater than or equal to 5 years). A single isolate resistant to rifampin and rifampin-trimethoprim was encountered. The eradication rate achieved with this regimen of rifampin-trimethoprim was too low to recommend its routine use. However, a higher dose or longer course might merit clinical trial.
Prospective comparison of amoxicillin-clavulanic acid and cefaclor in treatment of uncomplicated urinary tract infections
Authors: Gurwith M J , Stein G E , Gurwith D
Published: June 2012

Patients with acute, uncomplicated urinary tract infections were treated with either amoxicillin-clavulanic acid (A-C) in fixed combination or cefaclor for 10 days in a prospective randomized comparison. The A-C group included 29 women and 1 man (mean age, 25.5 years), and the cefaclor group included 35 women and 1 man (mean age, 24.9 years). The cure rates were 26 (87%) of 30 with A-C and 26 (72%) of 36 with cefaclor (P greater than 0.20). There was one failure in each group, each caused by an isolate resistant to ampicillin. There were one relapse and two reinfections in the A-C group, compared with seven relapses and two reinfections in the cefaclor group. Side effects, including patients started on antibiotics but whose cultures did not confirm urinary tract infections, were diarrhea in 7 (16%) and rash in 1 (2%) of 44 A-C patients, compared with diarrhea in 1 (2%) and yeast vaginitis in 3 (6%) of 48 cefaclor patients. Although the A-C group had a greater proportion of antibody-coated bacterium-positive infections (22 versus 18 with cefaclor), there was a lower recurrence rate with fewer relapses in patients treated with A-C.
Effect of phosphate and amino acids on echinomycin biosynthesis by Streptomyces echinatus
Authors: Formica J V , Waring M J
Published: June 2012

Streptomyces echinatus produces only echinomycin (quinomycin A), in contrast to other streptomycetes, which produce families of quinoxaline antibiotics differing in the amino acid composition of the oligopeptide (quinomycins A, B, B0, C, D, and E) or the structure of the sulfur-containing cross bridge (triostins A, B, and C). Attempts were made to establish conditions for directed biosynthesis with S. echinatus. The lability of the peptide lactone to alkaline pH was obviated by using high levels of phosphate or HEPES [4-(2-hydroxyethyl)-1-piperazineethane-sulfonic acid] buffer in the production medium. Maintaining the pH below 7.5 resulted in an apparent stimulation of production. Amino acids which serve as structural components or as precursors of echinomycin were employed singly or in combination with nitrate in a chemically defined medium. Based on specific yield (micrograms of echinomycin per milligram of mycelia [dry weight]), D- and L-serine, D-alanine, L-valine, and L-phenylalanine produced equivalent yields of antibiotic which were approximately twofold greater than yields obtained with nitrate alone. In contrast, L-alanine, beta-alanine, and L-threonine produced a three- to fourfold stimulation of production. Although the other amino acids diminished antibiotic production, L-isoleucine, which ostensibly was inhibitory to production, supported the accumulation of a quinoxaline antibiotic in which the cross-bridge sulfur lacked a methyl group.
In vitro activity of enoxacin, a quinolone carboxylic acid, compared with those of norfloxacin, new beta-lactams, aminoglycosides, and trimethoprim
Authors: Chin N X , Neu H C
Published: June 2012

Enoxacin is a new quinolone carboxylic acid compound. Its activity against 740 bacterial isolates was determined. It inhibited 90% Escherichia coli, Klebsiella sp., Aeromonas sp., Enterobacter spp., Serratia spp., Proteus mirabilis, and Morganella morganii at less than or equal to 0.8 micrograms/ml. The majority of Pseudomonas aeruginosa was inhibited by less than or equal to 3.1 micrograms/ml. Haemophilus spp. and Neisseria spp. were inhibited by less than 0.1 micrograms/ml. Although most Staphylococcus aureus were inhibited by 3.1 micrograms/ml, some streptococcal species had minimal inhibitory concentrations of 6.3 to 12.5 micrograms/ml and Bacteroides sp. had minimal inhibitory concentrations greater than or equal to 25 micrograms/ml. Activity of enoxacin and norfloxacin was similar. Enoxacin inhibited organisms resistant to cefotaxime, moxalactam, gentamicin, and piperacillin. Enoxacin was less active in urine at an acid pH than in broth, but serum did not decrease minimal inhibitory concentrations or minimal bactericidal concentrations. There was no major difference between minimal inhibitory concentrations and minimal bactericidal concentrations. Resistance frequency development was less than 10(-9) for most bacterial species.
Error rates associated with the use of recently proposed breakpoints for testing Pseudomonas aeruginosa versus gentamicin, tobramycin, and amikacin by the standardized disk agar diffusion test
Authors: Woolfrey B F , Fox J M , Quall C O , Lally R T
Published: June 2012

Two hundred fifteen Pseudomonas aeruginosa isolates were tested in parallel by the disk agar diffusion test, using a standardized agar preparation, and by a microbroth test, using dilutions differing by small arithmetic increments. For gentamicin, recently proposed breakpoints of resistance (R) less than or equal to 12 mm and susceptibility (S) greater than or equal to 16 mm produced error rates of 20 and 6.8%, respectively. Limiting the error rate for susceptible interpretations to less than or equal to 2% produced a widening of the intermediate zone to include 67.4% of the isolates tested. For tobramycin, the recently proposed breakpoints of R less than or equal to 12 mm and S greater than or equal to 15 mm were associated with error rates of 66.7 and 1.4%, respectively. Breakpoints of R less than or equal to 12 mm and S greater than or equal to 13 mm were demonstrated to be equally effective when the error rate for susceptible interpretations was limited to less than or equal to 2% by error rate-bound analysis. For amikacin, proposed breakpoints of R less than or equal to 14 mm and S greater than or equal to 17 mm were associated with error rates of 27.3 and 3.2%, respectively. Limiting the error rates for susceptible interpretations to less than or equal to 2% required breakpoints of R less than or equal to 14 mm and S greater than or equal to 18 mm. The ability to establish effective susceptibility breakpoints for tobramycin and amikacin appeared not to be related to the disk agar diffusion test process itself but rather to the high degree of susceptibility of the P. aeruginosa population. These findings severely limit the usefulness of the disk agar diffusion procedure for testing P. aeruginosa versus the aminoglycosides. For this purpose, we recommend dilution tests which employ small arithmetic increment schemes.