bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of moxalactam (LY127935) susceptibility tests by disk diffusion and agar plate dilution methods
Authors: Hall W H , Opfer B J
Published: June 2012

Susceptibility of pathogenic aerobic bacteria to moxalactam (LY127935) was compared by two methods, diffusion from 30-microgram disks and agar plate dilution. The two methods gave a satisfactory degree of correlation when compared by linear regression, but the slope of the linear regression was significantly steeper for gram-negative bacilli (Enterobacteriaceae and Pseudomonas aeruginosa) than for coccal organisms (streptococci and staphylococci). The largest zone diameters by disk diffusion were found with Citrobacter, Proteus, Escherichia coli, Klebsiella, and Enterobacter strains. The error rate-bounded method of Metzler and DeHaan (J. Infect. Dis. 130:588-594, 1974) gave useful breakpoints of disk zone sizes for moxalactam resistance and susceptibility.
Comparison of the effects of arabinosyladenine, arabinosylhypoxanthine, and arabinosyladenine 5'-monophosphate against herpes simplex virus, varicella-zoster virus, and cytomegalovirus with their effects on cellular deoxyribonucleic acid synthesis
Authors: Gephart J F , Lerner A M
Published: June 2012

In a single line of human foreskin fibroblasts, minimum inhibitory concentrations (MICs) and the minimum intracellular virus inactivation concentrations (MIICs) of arabinosyladenine, arabinosylhypoxanthine, and arabinosyladenine 5'-monophosphate were assayed for a number of recent isolates of herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), and cytomegalovirus (CMV). (The term MIIC is used here to describe the selective qualitative intracellular inhibition of the virus inoculum in the primary tissue cultures. The inoculum is not recoverable in subcultures free of antiviral agent.) MICs and MIICs of each of the antiviral agents were readily obtained for each strain of HSV-1, HSV-2, and VZV tested, but all seven strains of CMV tested were much more resistant. At the endpoint, there was little variation in the MICs or MIICs among strans of the same virus. Final MIC results for HSV-1 and HSV-2 were complete after 3 days of incubation; CMV and VZV results required as long as 6 days. The MIC for each herpesvirus increased with incubation, but at the endpoint the MIC and MIIC were approximately equal. VZV was most susceptible to each drug, followed by HSV-1 and HSV-2. The latter two viruses were quite similar. There was no difference in antiviral susceptibilities among any of the strains of HSV-1, HSV-2, VZV, or CMV tested. The toxicities of arabinosyladenine, arabinosylhypoxanthine, and arabinosyladenine 5'-monophosphate were simultaneously compared by using both microscopic cytotoxicity and inhibition of uptakes of [14C]thymidine into cellular deoxyribonucleic acid and of 14C-labeled amino acids into protein. The selective inhibition of each antiviral agent against viral and cellular deoxyribonucleic acid polymerases was confirmed. Simultaneous assays of antiviral and anticellular activities of antiviral agents may be useful in projecting further in vivo experiments.
N-formimidoyl thienamycin (MK0787): in vitro study
Authors: Shadomy S , May R S
Published: June 2012

N-Formimidoyl thienamycin (MK0787) was compared in vitro with three other beta-lactam and two aminoglycoside antibiotics. It was second in activity only to cefotaxime against members of the Enterobacteriaceae and to amikacin against Pseudomonas species. It was the most active antibiotic against Staphylococcus aureus. Resistance (minimal inhibitory concentration, greater than 128 microgram/ml) to N-formimidoyl thienamycin was not observed.
Resistance among fecal flora of patients taking sulfamethoxazole-trimethoprim or trimethoprim alone
Authors: Guerrant R L , Wood S J , Krongaard L , Reid R A , Hodge R H
Published: June 2012

Because of the widespread occurrence of resistance to sulfonamides among Enterobacteriaceae, some researchers have suggested using trimethoprim (TMP) alone instead of the combination sulfamethoxazole-trimethoprim (SMX-TMP) in treating infections with TMP-susceptible organisms. To answer whether SMX-TMP suppresses the emergence of resistant organisms compared with TMP alone, quantitative fecal cultures were made for total and TMP-resistant organisms before, during, and after SMX-TMP (800/160 mg twice a day) or TMP (200 or 100 mg twice a day) was given to 48 patients for 4 weeks in a prospective, randomized study. All three regimens left anaerobes intact and reduced the total aerobic coliform fecal flora by approximately 4 logs throughout the 4-week treatment period. In 11 of 19 (58%) patients taking TMP 200 mg twice daily, TMP-resistant organisms emerged or increased during therapy (P less than 0.01, compared with none of the 12 controls), whereas in only 4 of 18 (22%) patients on SMX-TMP did TMP-resistant organisms increase. These TMP-resistant organisms increased by less than 1 log and were predominantly Pseudomonas and Acinetobacter species. In only one instance did an SMX-TMP-resistant Escherichia coli strain emerge after 4 weeks of SMX-TMP therapy. The slight increase in Pseudomonas and Acinetobacter species seen with TMP alone in this study raises a potential risk of giving TMP alone in settings where these organisms may cause serious infections, as in immunosuppressed patients.
Evaluation of ceforanide as treatment for staphylococcal and streptococcal endocarditis
Authors: Cooper R H , Savitch C B , Joseph W P , Mills J
Published: June 2012

Ceforanide administered parenterally twice daily was used as the sole agent to treat 17 patients with right-sided endocarditis due to Staphylococcus aureus or nonenterococcal streptococci. Fifteen patients were cured of their original infection. Two patients were withdrawn from the study. One patient was transferred to another hospital 4 days after ceforanide therapy was initiated, and the other was changed to a different antibiotic regimen when his viridans streptococcus proved tolerant to ceforanide. The intramuscular form of ceforanide was well tolerated. It was stopped in two patients after week 3 of therapy because of adverse effects, possibly related to the study drug. These findings resolved with discontinuation of the ceforanide, and no additional antimicrobial therapy was necessary. Two patients who continued to abuse drugs intravenously during the study developed bacteremia with new organisms and required additional antimicrobial therapy. Ceforanide proved to be a useful agent in the treatment of right-sided endocarditis due to susceptible S. aureus and nonenterococcal streptococci.
Effect of antibiotics on the prevalence of enterotoxigenic Escherichia coli in two populations in the Philippines
Authors: Echeverria P , Mejia P A , Duangmani C
Published: June 2012

Hostesses and restaurant employees in the Philippines were studied to determine whether an increased use of antibiotics was associated with a higher point prevalence of enterotoxigenic Escherichia coli. Of 1,030 hostesses and 628 restaurant employees, 28 and 4%, respectively, said that they had taken antibiotics within a week of being cultured (P less than 0.001). Of hostesses and restaurant employees, 10% (103 of 1,030) and 2% (14 of 628), respectively, had antibiotics detectable in their urine (P less than 0.001). Enterotoxigenic E. coli strains were isolated from 1.2% (12 of 1,030) of hostesses and 1.7% (11 of 628) of restaurant employees. In both populations, enterotoxigenic E. coli strains were never found in subjects who had antibacterial activity in their urine. Although resistance to two or more antibiotics was found more frequently in E. coli isolated from hostesses than in that isolated from restaurant workers (48 versus 33%; P less than 0.01), antibiotic selective pressure did not increase the prevalence of enterotoxigenic E. coli in these two populations.
Comparative pharmacokinetics of cefoperazone and cefamandole
Authors: Srinivasan S , Francke E L , Neu H C
Published: June 2012

The pharmacokinetics of cefoperazone, a new beta-lactam antibiotic, were studied in normal volunteers and compared with the pharmacokinetics of cefamandole. After a 30-min infusion of 2 g of cefoperazone, the mean serum level was 256 micrograms/ml; at 4 h, the serum level was 20 micrograms/ml, and at 24 h, the level was 1.25 micrograms/ml, compared with levels of cefamandole of 188 micrograms/ml at the end of infusion, 1.8 micrograms/ml at 4 h, and none detected thereafter. The mean half-life of cefoperazone was 1.6 h, compared with 0.7 h for cefamandole. The area under the curve was 356 micrograms/ml per h for cefoperazone, which was three times that for cefamandole. The apparent volume of distribution for cefoperazone was 9.9 liters/1.73 m2 compared with 12.5 liters/1.73 m2 for cefamandole. Serum clearance of cefoperazone was 85 ml/min, and renal clearance was 25 ml/min, compared with a serum clearance of 224 ml/min and a renal clearance of 213 ml/min for cefamandole. Urine levels exceeded 25 micrograms/ml in the first 8 h after injection. Renal recovery of cefoperazone was only 29%.
Pharmacokinetics of moxalactam and cefazolin compared in normal volunteers
Authors: Srinivasan S , Fu K P , Neu H C
Published: June 2012

The pharmacokinetics of moxalactam, a new beta-lactam antibiotic with an unusually broad spectrum of activity, were studied in normal volunteers and compared with the pharmacokinetics of cefazolin. After a 1,000-mg intramuscular injection of moxalactam, a mean peak serum level of 49 +/- 10 micrograms/ml was achieved at 30 to 60 min which was equivalent to the level achieved with 0.5 g of cefazolin. Serum levels of 4.57 +/- 0.63 micrograms/ml, above the inhibitory levels for most organisms, were present at 8 h. The half-life of moxalactam was 2.3 h. After a 30-min intravenous infusion of 1 g, the serum level of moxalactam was 60 +/- 18.8 micrograms/ml. This compares with a serum level of 70 micrograms/ml obtained with an infusion of 0.5 g of cefazolin. At 6 h, 3.59 +/- 0.68 microgram/ml of moxalactam was present. The half-life of moxalactam was 2.3 h, similar to that of cefazolin. By 1 h after administration, serum levels of moxalactam were higher after intramuscular administration than after intravenous delivery. Urinary recovery of the drug was 76% after intramuscular injection and 74% after intravenous infusion, with the majority of the drug having been excreted in the first 4 h after administration. Urinary recovery of cefazolin was 85%. The pharmacokinetics of moxalactam are similar to those of cefazolin.
Biliary concentrations of piperacillin in patients undergoing cholecystectomy
Authors: Giron J A , Meyers B R , Hirschman S Z
Published: June 2012

Piperacillin is a new semisynthetic, expanded-spectrum penicillin with marked activity against Pseudomonas aeruginosa. The biliary excretion of piperacillin was studied in patients undergoing cholecystectomy. Concentrations of piperacillin in common duct bile at 35 to 90 min postinfusion of 1-g doses ranged from 31 to 920 micrograms/ml, with a mean (+/- standard deviation) of 467 +/- 363 micrograms/ml. Gallbladder piperacillin levels at 30 to 75 min postinfusion ranged from 2.2 to 80 micrograms/ml, with a mean of 27 +/- 31 micrograms/ml. No correlation occurred with peak serum level of antibiotic, creatinine, bilirubin, or alkaline phosphatase. Significant amounts of piperacillin were excreted via the biliary system.
Comparative synergistic activity of cefoperazone, cefotaxime, moxalactam, and carbenicillin, combined with tobramycin, against Pseudomonas aeruginosa
Authors: Mintz L , Drew W L
Published: June 2012

A broth dilution checkerboard synergy assay was used to assess the activity of cefoperazone, cefotaxime, moxalactam, and carbenicillin, in combination with tobramycin, against 38 strains of Pseudomonas aeruginosa. Synergy occurred significantly more often (P less than 0.001) when tobramycin was combined with cefotaxime (63%) than when it was combined with carbenicillin (26%), cefoperazone (21%), or moxalactam (18%). Of the 25 synergistically inhibited strains, the combination cefotaxime-tobramycin was synergistic against 24 and was the only synergistic combination against 10. Of six strains initially resistant to cefotaxime, five were susceptible to this agent (minimum inhibitory concentration, less than or equal to 32 micrograms/ml) when it was combined with tobramycin. Clinical trials are needed to determine the therapeutic efficacy of cefotaxime-aminoglycoside combinations in the treatment of serious Pseudomonas infections.
In vivo antimycotic activity of naftifine
Authors: Petranyi G , Georgopoulos A , Mieth H
Published: June 2012

Naftifine, a new antifungal agent belonging chemically to the allylamines, was tested for its in vivo activity after topical application against guinea pig skin infections caused by Trichophyton mentagrophytes, T. mentagrophytes var. quinckeanum, or Microsporum racemosum. Compared with standard compounds, naftifine proved to be highly effective mycologically and clinically after topical application in the above models.
In vitro activity of N-formimidoyl thienamycin in comparison with cefotaxime, moxalactam, and ceftazidime
Authors: Verbist L , Verhaegen J
Published: June 2012

The in vitro activity of N-formimidoyl thienamycin (N-f-thienamycin) was compared with the activities of other B-lactam antibiotics, using over 500 clinical bacterial isolates. N-f-Thienamycin inhibited 90% of the isolates of the common Enterobacteriaceae between 0.006 and 2 microgram/ml, regardless of their resistance to amoxicillin, ticarcillin, or cephalothin. It was, however, fourfold less active than moxalactam and ceftazidime and eightfold less active than cefotaxime. N-f-Thienamycin was nearly as active as ceftazidime against Pseudomonas aeruginosa (mean minimal inhibitory concentration, 3.0 microgram/ml) and eightfold more active than cefotaxime and moxalactam. In contrast to cefotaxime, moxalactam, and ceftazidime, N-f-thienamycin was highly active against enterococci (mean minimal inhibitory concentration, 1.3 microgram/ml) and staphylococci. The oxacillin-susceptible Staphylococcus aureus were inhibited between 0.03 and 0.12 microgram/ml, and the oxacillin-resistant S. aureus were inhibited between 0.12 and 2 microgram/ml. The high activity of N-f-thienamycin against both of the most important gram-positive and gram-negative organisms makes it a very promising new antibiotic.
Piperacillin pharmacokinetics in subjects with chronic renal failure
Authors: Thompson M I , Russo M E , Matsen J M , Atkin-Thor E
Published: June 2012

The pharmacokinetic parameters of piperacillin sodium were studied in eight volunteer subjects with chronic renal failure. Subjects were given a single 30-min intravenous infusion of 70 mg/kg (lean body weight) on their off-dialysis day. Blood was drawn from the contralateral arm at 15 and 30 min and 1, 3, 6, 9, and 12 h from the start of the infusion. Kinetic parameters were determined during the elimination phase with a one-compartment open model for linear kinetics. The following pharmacokinetic parameters (mean +/- standard deviation) were determined for the eight subjects: elimination half-life = 3.33 +/- 0.99 h, elimination rate constant = 0.22 +/- 0.06 h-1, apparent volume of distribution = 0.18 +/- 0.05 liters per kg, and total body clearance = 0.041 +/- 0.019 liters per kg/h. The mean peak serum concentration was 372 +/- 125 microgram/ml, and mean trough at 12 h was 39 +/- 27 microgram/ml. A dose of 70 mg/kg (lean body weight) or a dose of 4 g appears to provide adequate serum concentrations against susceptible organisms for a 12-h interval. No adverse reactions were noted in any subject throughout the study.
Antimicrobial Activity of Cefmenoxime (SCE-1365)
Authors: Stamm John M. , Girolami Roland L. , Shipkowitz Nathan L. , Bower Robert R.
Published: June 2012

The in vitro activity of cefmenoxime (SCE-1365 or A-50912), a new semisynthetic cephalosporin antibiotic, was compared with those of cefazolin, cefoxitin, and cefamandole against a broad spectrum of 486 organisms and with that of cefotaxime against 114 organisms. Cefmenoxime and cefotaxime exhibited nearly equivalent activities against those organisms tested and were the most active of these cephalosporins against all aerobic and facultative organisms except
Staphylococcus aureus
. The minimum inhibitory concentration (MIC) of cefmenoxime required to inhibit at least 90% of strains tested (MIC
90
) ranged from 0.06 to 8 μg/ml for the
Enterobacteriaceae
. The MIC
90
s for gram-positive cocci were 0.015 and ≤0.008 μg/ml for
Streptococcus pneumoniae
and
Streptococcus pyogenes
, respectively, and 2 μg/ml for
S. aureus
. Group D streptococci were less susceptible. Cefmenoxime was very active against
Haemophilus influenzae, Neisseria gonorrhoeae
, and
Neisseria meningitidis
with MIC
90
s ranging from ≤0.008 to 0.25 μg/ml. Cefmenoxime, at a concentration of 16 μg/ml, inhibited 78% and 73% of
Pseudomonas aeruginosa
and
Acinetobacter
spp., respectively. MICs for anaerobes ranged from 0.5 to >128 μg/ml with good activity against the gram-positive organisms. In addition, cefmenoxime activity was bactericidal and only slightly affected by differences in inoculum size. The combination of cefmenoxime and gentamicin was synergistic against 80% of the
Enterobacteriaceae
and 100% of
P. aeruginosa
strains tested. Development of resistance to cefmenoxime was slow or absent for organisms with low initial MICs but more rapid for those with higher initial MICs. Cefmenoxime exhibited good protective activity in mice infected with
Escherichia coli, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris
, or
S. aureus
but was less effective against
P. aeruginosa
.
Penetrance of nafcillin into human ventricular fluid: correlation with ventricular pleocytosis and glucose levels
Authors: Yogev R , Schultz W E , Rosenman S B
Published: June 2012

Fourteen hydrocephalic pediatric patients with suspected shunt infections were studied for penetrance of nafcillin into the ventricular fluid after intravenous administration. In seven patients with bacterial ventriculitis, the concentration of nafcillin in ventricular fluid was 0.8 to 20.4% of the peak concentration in serum. In the remaining seven patients without bacterial ventriculitis, ventricular fluid levels ranged between less than or equal to 0.02 to 4% of peak serum concentrations. Although the degree of pleocytosis correlated poorly with penetrance, ventricular fluid glucose levels correlated inversely with penetrance of nafcillin (r = -0.7275, P less than 0.001).
Inhibition of Escherichia coli by thioglycerol
Authors: Jensen K K , Javor G T
Published: June 2012

Thioglycerol inhibits the growth of various Escherichia coli strains and other microorganisms, both gram positive and gram negative. The susceptibility of organisms varies. The bactericidal action of this substance is not continuous and stops after an initial burst. At subbactericidal concentrations synthesis of ribonucleic acid is the most strongly affected. This is not due to interference with nucleoside biosynthesis or to direct inhibition of ribonucleic acid polymerase by thioglycerol.
Penicillin-binding proteins in Haemophilus influenzae
Authors: Makover S D , Wright R , Telep E
Published: June 2012

The penicillin-binding proteins (PBPs) of Haemophilus influenzae were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Eight major PBPs, ranging in molecular weights from 90,000 to 27,000, were detected. The pattern of molecular weights was different from that determined fro Escherichia coli or Pseudomonas aeruginosa. A study on the binding of several beta-lactam antibodies to the PBPs at their minimal inhibitory concentrations and at lower and higher concentrations revealed that all had highest affinity for PBP 2. Amdinocillin (mecillinam) was an exception; it had highest affinity for PBP 3. The morphological effects of several penicillins, cephalosporins, and amdinocillin on H. influenzae were similar to those reported for E. coli.
Altered penicillin-binding proteins in methicillin-resistant strains of Staphylococcus aureus
Authors: Hartman B , Tomasz A
Published: June 2012

The penicillin-binding proteins (PBPs) of a methicillin-resistant (MR) and a methicillin-susceptible (MS) Staphylococcus aureus were compared by various approaches involving the use of high-specific-activity [3H]penicillin as a reagent. The MR and MS strains were found to contain PBPs of the same number and electrophoretic mobilities. However, saturation of PBPs 1, 2, and 3 by methicillin in the MR strain required the use of several thousands of micrograms of antibiotic per milliliter, whereas 0.2 to 0.4 micrograms of methicillin per ml was sufficient to effectively compete with [3H]penicillin for the PBPs for the MS strain. Additional experiments indicate that these differences most likely reflect a greatly decreased affinity of the PBPs of the MR strain as compared to those of the MS strain. Shift of the pH of the culture medium of the MR strain from pH 7.0 to 5.2 resulted in an immediate drop in phenotypic resistance to methicillin (from a minimal inhibitory concentration value of 3,200 micrograms/ml at pH 7.0 to 0.8 microgram/ml at pH 5.2). Examination of the methicillin affinities of PBPs in MR bacteria grown at pH 5.2 showed the presence of the same low-affinity PBPs as in bacteria grown at pH 7.0. Thus, the pH-dependent resensitization to methicillin cannot be explained by a parallel increase in the antibiotic affinities of the PBPs.
Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects
Authors: Nilsson-Ehle I , Ursing B , Nilsson-Ehle P
Published: June 2012

We developed methods for measuring metronidazole, its two major metabolites, and tinidazole in serum and urine. After treatment of each sample with an equal volume of 5% perchloric acid, the drugs were separated by reverse-phase high-pressure liquid chromatography (retention times, 6 to 18 min). Quantitation was based on spectrometry at 320 nm. These assays were sensitive, rapid, and specific, and recoveries from biological samples were quantitative. Metronidazole and tinidazole were given as rapid intravenous infusions to four healthy human volunteers. The biological half-lives of these two compounds were 5.4 and 11.1 h, respectively. The hydroxy metabolite of metronidazole appeared quickly in serum and was eliminated at a slow rate. The acetic acid metabolite of metronidazole was detected in serum at very low levels and only for a limited time. No metabolic products of tinidazole were found in serum samples. In urine, 43.7% of the administered dose of metronidazole was recovered over a period of 24 h (24.1% of the dose as the hydroxy metabolite, 12.0% as the acetic acid metabolite, and 7.6% as unchanged drug). Only 18.4% of the infused dose of tinidazole was eliminated in urine over a period of 72 h, and no metabolic products were detected.
Gingival crevicular fluid levels of clindamycin compared with its minimal inhibitory concentrations for periodontal bacteria
Authors: Walker C B , Gordon J M , Cornwall H A , Murphy J C , Socransky S S
Published: June 2012

Clindamycin concentrations in gingival crevicular fluid and in blood were determined over a 7-h period and were related to the minimal inhibitory concentrations of this agent for 340 bacterial strains isolated from diseased periodontal sites. The clindamycin levels after administration of single 300-mg oral doses were measured in gingival crevicular fluids by using an agar diffusion bioassay. Minimal inhibitory concentrations were determined by agar dilution techniques for 30 species of periodontal bacteria. With the exception of Eikenella corrodens and Actinobacillus actinomycetemcomitans, most of the bacteria were inhibited by a concentration of 1.0 microgram of clindamycin per ml or less. The peak concentrations in crevicular fluid (2.0 +/- 0.3 microgram/ml) and in blood (1.9 +/- 0.3 micrograms/ml) were approximately the same. However, crevicular fluid levels of 1.0 micrograms/ml and above were present for up to 6 h, whereas blood concentrations dropped below 1.0 micrograms/ml within 2 h after administration. Based on its minimal inhibitory concentrations, clindamycin at crevicular fluid levels of 1.0 micrograms/ml or above should inhibit most bacteria associated with diseased periodontal sites.
Evaluation of a new latex agglutination inhibition card test for determining serum gentamicin levels
Authors: Doern G V , Glew R H , Parker D S , Pavuk R A , Brown S D
Published: June 2012

A new latex agglutination inhibition card test was compared with a microbiological method and radioimmunoassay for determining serum gentamicin levels. When 60 sera, each containing a known concentration of gentamicin, were analyzed by the microbiological method and by radioimmunoassay, both methods were found to yield accurate and precise results. Analysis of the same 60 sera with the latex agglutination inhibition card test revealed significant variability over a wide range of serum gentamicin concentrations.
Procedure for Assay of Tobramycin in Serum Containing Moxalactam
Authors: Mahoney David F. , Butler T. F. , Turner J. R.
Published: June 2012

Moxalactam was examined as a substrate for 11 β-lactamases. Hydrolysis was shown only with the β-lactamase from
Bacillus cereus
, a nonpathogenic bacterium. Tobramycin was assayed in tobramycin-moxalactam mixtures by using this β-lactamase.
Interaction Between Vancomycin and Rifampin Against
Staphylococcus aureus
Authors: Watanakunakorn Chatrchai , Guerriero JoAnn C.
Published: June 2012

By the time-kill method, vancomycin and rifampin were antagonistic against 43 of 50 strains of
Staphylococcus aureus
, whether susceptible or resistant to methicillin.
In Vitro Antimicrobial Activity of Ceftizoxime Against Glucose-Nonfermentative Gram-Negative Rods
Authors: Yabuuchi Eiko , Ito Tomiyoshi , Tanimura Eiki , Yamamoto Norimi , Ohyama Akio
Published: June 2012

Ceftizoxime, a new cephalosporin, was active against
Pseudomonas cepacia, Flavobacterium meningosepticum, Alcaligenes faecalis
, and
Acinetobacter calcoaceticus
and was more potent against
Pseudomonas aeruginosa
and
Pseudomonas putida
than was carbenicillin.
Fluorimetric determination of cefuroxime in body fluids
Authors: Al-Rawi Z H , Tabaqchali S
Published: June 2012

A simple and accurate fluorimetric procedure for measuring cefuroxime in body fluids is described. A fluorescent product was produced by addition of hydrochloric acid, heating, and cooling, followed by addition of sodium hydroxide and further heating at 100 degree C. The fluorescence intensity of the final solution was measured in a fluorimeter at an excitation wavelength of 375 nm and an emission wavelength of 440 nm and related to the antibiotic concentration. Thin-layer chromatography of the final solution showed a single fluorescent spot (Rf value, 0.6). Freedom from interference from other therapeutic agents and endogenous substances, as well as the close correlation between this method and the standard microbiological assay method, was demonstrated. The simplicity and reliability of the fluorimetric assay method make it particularly suitable for clinical use.
Antiherpesviral and anticellular effects of 1-beta-D-arabinofuranosyl-E-5-(2-halogenovinyl) uracils
Authors: Machida H , Sakata S , Kuninaka A , Yoshino H
Published: June 2012

1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl) uracil (BV-ara-U) and 1-beta-D-arabinofuranosyl-E-5-(2-chlorovinyl)uracil (CV-ara-U) were tested for their anti-herpesviral activity in virus rating method, a plaque reduction method, and a virus yield reduction method, using human embryonic lung fibroblast (HEL-F) cells, At a concentration as low as 0.1 microgram/ml, both drugs exerted a marked inhibitory effect on the development of cytopathogenic effect induced by herpes simplex virus type 1 (HSV-1) infection and on the multiplication and plaque formation of HSV-1. Neither BV-ara-U nor CV-ara-U was significantly active against HSV type 2 (HSV-2). They scarcely inhibited growth of HEL-F cells, mouse L, and murine leukemia cells. Compared with 1-beta-D-arabinofuranosylthymine and 5-iodo-deoxyuridine, BV-ara-U and CV-ara-U were more than 10 times as active against HSV-1 and much less active against HSV-2. BV-ara-U was as active as E-5-(2-bromovinyl)-2'-deoxyuridine against HSV-1 and less inhibitory to growth of HEL-F cells. Cellular deoxyribonucleic acid synthesis was not significantly influenced by the new derivatives of arabinosyluracil, even at a concentration as high as 300 microgram/ml. The derivatives showed extremely marked inhibition of deoxyribonucleic acid synthesis in HSV-1-infected cells, whereas their inhibitory effect on deoxyribonucleic acid synthesis in HSV-2-infected cells was much lower than that in HSV-1-infected cells. These findings indicate that BV-ara-U and CV-ara-U are selectively inhibitory to HSV-1 multiplication.
Production of high levels of human leukocyte interferon from a continuous human myeloblast cell culture
Authors: Familletti P C , McCandliss R , Pestka S
Published: June 2012

A myeloblast cell line has proved to be an excellent source of human leukocyte interferon. These cells, primed with interferon and induced with Sendai virus, produced optimal levels of human leukocyte interferon. The cells grew readily in spinner flasks and in medium containing horse serum. Interferon production over several months yielded an average titer of 2 X 10(5) reference units of interferon per 10(7) cells. The interferon produced by these cells appeared to be predominantly species of human leukocyte interferon. Since these cells seemed to consist of myeloblasts, it is clear that cells other than B-lymphocytes can produce leukocyte interferon.
Bactericidal activity of cefoperazone with CP-45,899 against large inocula of beta-lactamase-producing Haemophilus influenzae
Authors: Yu P K , Washington J A
Published: June 2012

Bactericidal activity of cefoperazone, alone and in combination with the beta-lactamase inhibitor CP-45,899, was tested against inocula of 10(7) colony-forming units of beta-lactamase-producing isolates of Haemophilus influenzae type b per ml. Of 19 strains tested, 10 required greater than or equal to 64 microgram of cefoperazone per ml for killing, whereas no strains were killed by less than 64 microgram of CP-45,899 per ml. Synergy occurred with the combination of 4 microgram of each agent per ml against 9 of the 10 cefoperazone-resistant strains.
Quantitative susceptibility test methods in major United States medical centers
Authors: Murray P R , Jorgensen J H
Published: June 2012

To assess the current trend toward performance of routine quantitative susceptibility test methods, we surveyed microbiology laboratories in 41 major U.S. medical centers. Agar dilution and microdilution tests were used primarily by those laboratories routinely performing numerous minimal inhibitory concentration tests and few or no minimal bactericidal concentration tests. Macrotube dilution tests were used by laboratories performing relatively few minimal inhibitory concentration tests, but routinely performing minimal bactericidal concentration tests. Major methodological variations were reported by the surveyed laboratories and including: (i) preparation and storage of antimicrobial solutions, (ii) standardization and concentration of the test inoculum, (iii) interpretation of minimal inhibitory concentration endpoints, and (iv) determination of the antibiotic concentration required to be bactericidal. The results of this survey indicate that significant variations in test methods exist, even though quantitative susceptibility tests are commonly used.
Trimethoprim-sulfamethoxazole therapy of experimental Escherichia coli meningitis in rabbits
Authors: Mylotte J M , Bates T R , Sergeant K A , Matson R E , Beam T R
Published: June 2012

We used two strains of ampicillin-susceptible Escherichia coli to produce meningitis in rabbits and utilized these models (i) to compare the killing effects of parenteral trimethoprim-sulfamethoxazole (TMP-SMZ) and ampicillin on E. coli in cerebrospinal fluid after 8 h of treatment and (ii) to measure the penetration of TMP-SMZ and ampicillin into cerebrospinal fluid and the brain. At 16 h after intracisternal inoculation with a test strain, rabbits were treated with TMP (6 mg/kg per h) and SMZ (30 mg/kg per h), ampicillin (40 mg/kg per h), or saline intravenously for 8 h. TMP-SMZ levels were measured by high-pressure liquid chromatography, and ampicillin levels were measured by microbiological assay. Mean +/- standard deviation concentrations of TMP, SMZ, and ampicillin in cerebrospinal fluid (mean percent penetration) at the completion of 8 h of therapy were 0.80 +/- 0.41 (18%), 15.7 +/- 21.1 (27.2%), and 2.6 +/- 1.7 (8.9%) microgram/ml, respectively. TMP, SMZ, and ampicillin levels in brain homogenate after 8 h of therapy were 0.23 +/- 0.07 (6.6%), 3.31 +/- 3.3 (5.5%), and 0.6 +/- 4.53 (1.9%) microgram/g, respectively. TMP-SMZ infusion for 8 h produced a significant reduction in mean bacterial counts in cerebrospinal fluid in both models of meningitis compared with saline controls. The decrease in mean bacterial counts with TMP-SMZ therapy was equivalent to that produced by ampicillin.
Effect of penicillin G on release of peptidoglycan fragments by Neisseria gonorrhoeae: characterization of extracellular products
Authors: Sinha R K , Rosenthal R S
Published: June 2012

The effect of penicillin G (penG) on the turnover and release of peptidoglycan (PG) by Neisseria gonorrhoeae RD5 was investigated. We previously showed that exponentially growing gonococci (labeled in the glycan moiety with glucosamine and muramic acid and in the peptide with diaminopimelic acid) turn over ca. 35% of their PG per generation. In current studies, addition of penG accelerated the rate of PG hydrolysis by more than twofold and resulted in a corresponding increase in the amount of soluble PG fragments found in the medium. This increase of soluble PG was accounted for mainly by the release of nonreducing (anhydro-muramyl-containing) disaccharide peptide dimers (molecular weight, about 2,000) and trimers that were composed of subunits, linked not by peptide cross-linking bonds, but probably only by glycosidic bonds. The enhanced release of these products suggested that penG, directly or indirectly, stimulates the activity of a glycan-splitting, gonococcal PG:PG-6 muramyl transferase (transglycosylase). PG monomers that were released in the presence of penG were identical, both qualitatively and quantitatively, to the monomers released as a result of turnover in the absence of penG and consisted of anhydro-muramyl-containing disaccharide tripeptides and tetrapeptides. PenG-treated bacteria consistently released slightly less free disaccharide and free peptides than did control cultures, implying a penG-associated depression in the activity of the gonococcal N-acetylmuramyl-L-alanine amidase. In addition to stimulating the release of PG fragments, penG was also associated with greatly enhanced release from cells of glucosamine-containing non-PG macromolecule(s).
In vivo activity of ceftriaxone (Ro 13-9904), a new broad-spectrum semisynthetic cephalosporin
Authors: Beskid G , Christenson J G , Cleeland R , DeLorenzo W , Trown P W
Published: June 2012

Ceftriaxone (Ro 13-9904) was compared with other newer beta-lactam antibiotics for activity in experimental infections of mice with Enterobacteriaceae, Haemophilus influenzae, Pseudomonas aeruginosa, and gram-positive bacteria. Overall, ceftriaxone was equal or superior to cefotaxime and cefoperazone against systemic infections. All three drugs were highly potent against most organisms but were considerably less active against P. aeruginosa. However, ceftriaxone tended to be more active than the other two agents against 8 of the 10 P. aeruginosa strains tested. Ceftriaxone, cefmenoxime (SCE 1365), and moxalactam were all highly active against systemic infections with 16 strains of Enterobacteriaceae, whereas ceftriaxone was more active against infections with two strains of streptococci. When the drugs were administered at various time intervals before infection, ceftriaxone was superior to cefotaxime, cefmenoxime, and moxalactam. This suggested that ceftriaxone might be eliminated from mice more slowly than the other drugs. In the case of cefotaxime, this was directly confirmed by microbiological assays of plasma samples. In a murine meningitis model induced by Klebsiella pneumoniae or Streptococcus pneumoniae, ceftriaxone was more active than ampicillin or cefotaxime. Ceftriaxone was more active than ampicillin, cefotaxime, piperacillin, cefamandole, or carbenicillin in a pneumococcal, pneumonia model in mice. These studies indicate that ceftriaxone is a potent, broad-spectrum cephalosporin with unusual pharmacokinetic properties.
Rapid detection of chloramphenicol resistance in Haemophilus influenzae
Authors: Azemun P , Stull T , Roberts M , Smith A L
Published: June 2012

We compared a rigid (1-h) screening method for the detection of chloramphenicol acetyltransferase (CAT) activity with the standard spectrophotometric CAT assay to determine whether CAT-mediated chloramphenicol resistance in Haemophilus influenzae could be determined upon primary isolation. Of 58 H. influenzae cell sonicates, 28 had detectable CAT activity when the chloramphenicol-dependent production of free coenzyme A from acetyl coenzyme A was measured spectrophotometrically (standard method). These 28 strains were identified as producing CAT by the rapid method which uses lysed cell suspensions and a color change to detect CAT. The remaining 30 strains did not have CAT activity detectable by either method. This 1-h test for CAT should prove to be useful for the early presumptive identification of chloramphenicol resistance in H. influenzae.
Properties of
Streptomyces fradiae
Mutants Blocked in Biosynthesis of the Macrolide Antibiotic Tylosin
Authors: Baltz Richard H. , Seno Eugene T.
Published: June 2012

We isolated numerous mutants of
Streptomyces fradiae
blocked in tylosin biosynthesis after
N
-methyl-
N′
-nitro-
N
-nitrosoguanidine mutagenesis. These mutants were classified into nine groups, based upon the tylosin-like compounds produced and upon cofermentation analyses. More than 80% of the mutants isolated produced no tylosin-like compounds, and the majority of these were blocked only in the formation of tylactone. Four classes of mutants blocked in the biosynthesis or addition of tylosin sugars were isolated;
tylA
mutants were blocked in the formation of all three tylosin sugars, whereas
tylB, tylC
, and
tylD
mutants were blocked specifically in the biosynthesis or the addition of mycaminose, mycarose, and 6-deoxy-
d
-allose, respectively. Two classes of mutants (
tylH
and
tylI
) blocked in specific oxidations of tylactone and two classes (
tylE
and
tylF
) blocked in specific O-methylations of demethylmacrocin and macrocin were also characterized. Cofermentation and bioconversion studies with these mutants suggested the following relationships: (i) the tylosin sugars are derived from a common intermediate; (ii) tylactone is the first intermediate which can be excreted in appreciable quantities; (iii) the addition of mycaminose to the C-5 hydroxyl group of tylactone must precede oxidations at C-20 and C-23; (iv) oxidation at C-20 normally precedes the attachment of mycarose to the 4′ hydroxyl position of mycaminose; and (v) 6-deoxy-
d
-allose is added to the C-23 hydroxyl position of the lactone and subsequently O-methylated at 2‴ and 3‴ positions. The O-methylations appear to be the final two steps in tylosin biosynthesis, and the 2‴ O-methylation must occur before the 3‴ O-methylation can take place. All of the
tyl
mutants except the
tylG
mutants produced relatively high levels of tylosin-like intermediates or shunt products. Mutants blocked in specific steps other than 3‴ O-methylation, including a mutant blocked in 2‴ O-methylation of demethylmacrocin, produced normal levels of macrocin
O
-methyltransferase. Mutants apparently containing specific tylosin structural gene mutations produced normal levels of aerial mycelia and spores, produced low levels of tylosin aldehyde reductase, and were resistant to high levels of tylosin. However, three atypical
tylG
mutants produced no tylosin-like compounds, could not cosynthesize tylosin with any other
tyl
mutant, could not bioconvert tylactone or macrocin to tylosin, and produced no macrocin
O
-methyltransferase. These three mutants produced elevated levels of tylosin aldehyde reductase. In addition, one was very succeptible to tylosin and did not produce aerial mycelia or spores.
Comparative in vitro synergistic activity of new beta-lactam antimicrobial agents and amikacin against Pseudomonas aeruginosa and Serratia marcescens
Authors: Kurtz T O , Winston D J , Bruckner D A , Martin W J
Published: June 2012

The in vitro synergistic activities of moxalactam, cefoperazone, or cefotaxime in combination with amikacin or piperacillin were compared against aminoglycoside-susceptible and aminoglycoside-resistant isolates of Pseudomonas aeruginosa and Serratia marcescens by the checkerboard agar dilution method. All antimicrobial combinations demonstrated some synergy, and no antagonism was observed. Moxalactam plus amikacin and piperacillin plus amikacin were most frequently synergistic (two-thirds of the isolates inhibited synergistically by each combination), whereas combinations of moxalactam, cefotaxime, or cefoperazone with piperacillin were synergistic against only 18 to 25% of the isolates. Moxalactam plus amikacin was the combination most often synergistic for amikacin-susceptible P. aeruginosa, and piperacillin plus amikacin was the combination most frequently synergistic for amikacin-resistant P. aeruginosa and amikacin-susceptible S. marcescens. These results demonstrate frequent in vitro synergistic activity between the new beta-lactam agents and amikacin (especially moxalactam or piperacillin with amikacin), but comparative clinical trials are needed to establish the relative efficacy and toxicity of these combinations.
In vitro susceptibility of Capnocytophaga strains to 18 antimicrobial agents
Authors: Sutter V L , Pyeatt D , Kwok Y Y
Published: June 2012

Twenty-seven strains of capnocytophaga were tested for their susceptibility to 18 antimicrobial agents by an agar dilution technique. All strains were susceptible to achievable blood levels of penicillin G, cefaclor, cefoxitin, cefoperazone, moxalactam, clindamycin, chloramphenicol, and tetracycline. Most were susceptible to achievable levels of cefamandole, erythromycin, and metronidazole, and more than 10% were resistant to achievable levels of cephalexin and cephradine. With antimicrobial agents used in selective media, all strains were resistant to colistin, kanamycin, and nalidixic acid at commonly recommended concentrations of bacitracin and vancomycin.
Active uptake of tetracycline by membrane vesicles from susceptible Escherichia coli
Authors: McMurry L M , Cullinane J C , Petrucci R E , Levy S B
Published: June 2012

A major portion of tetracycline accumulation by susceptible bacterial cells is energy dependent. Inner membrane vesicles prepared from susceptible Escherichia coli cells concentrated tetracycline 2.5 to 5 times above the external concentration when the electron transport substrate D-lactate or reduced phenazine methosulfate was added. This stimulation was reversed by cyanide, 2,4-dinitrophenol, and carbonyl cyanide m-chlorophenyl hydrazone. These vesicles data showed that proton motive force alone could energize tetracycline uptake. The lactate-dependent uptake had a pH optimum of 6.9 and a magnesium optimum of 1 mM and was not saturable up to 400 microM tetracycline. Although the vesicles were not as active as cells in concentrating tetracycline, they were less active to a similar extent in concentrating tetracycline, they were less active to a similar extent in concentrating proline, the transport of which is known to be solely proton motive force dependent. Therefore, we concluded that the active uptake of tetracycline in susceptible cells was largely, if not solely, energized by proton motive force.
Moxalactam therapy of infections caused by cephalothin-resistant bacteria: influence of serum inhibitory activity on clinical response and acquisition of antibiotic resistance during therapy
Authors: Platt R , Ehrlich S L , Afarian J , O'Brien T F , Pennington J E , Kass E H
Published: June 2012

Thirty patients infected predominantly by Serratia marcescens and Pseudomonas aeruginosa were treated in an open trial with moxalactam, a broad-spectrum beta-lactam antibiotic. Twenty-three (76%) had a satisfactory microbiological or clinical response. Among 25 patients for whom serum inhibitory concentrations were measured, those with favorable microbiological responses had significantly higher values than those with poor responses (reciprocal geometric mean concentrations, 49 versus 4.9; P less than 0.01). A serum inhibitory concentration of greater than 1:8 correlated significantly with a favorable outcome (17 of 18 versus 2 of 7 responses; P less than 0.01). Although the overall clinical efficacy of moxalactam was good, resistant organisms of species identical to those of the original infecting isolates were recovered during therapy in seven cases, including five caused by Pseudomonas organisms and two caused by Serratia organisms.
Chloramphenicol transposons found in Salmonella naestved and Escherichia coli of domestic animal origin
Authors: Terakado N , Sekizaki T , Hashimoto K , Yamagata S , Yamamoto T
Published: June 2012

Salmonella naestved strain AHI-21, of calf origin, harbors a conjugative R plasmid of group H1, pTE21, which encodes resistance to chloramphenicol (Cm), tetracycline, streptomycin, and sulfadimethoxine. Escherichia coli strain AHI-1, of pig origin, also harbors a conjugative R plasmid of group I alpha, pTE1, which encodes resistance to chloramphenicol and trimethoprim. When either of these R plasmids coexisted with a nonconjugative plasmid, pMK1, which is a composite plasmid of ColE1 and a kanamycin transposon (Tn5), transposition of the Cmr gene into pMK1 occurred independently of the host recA gene function, indicating that both R plasmids contained Cm transposons, Tn3351 and Tn3352. Electron microscopic analysis of self-annealed and heteroduplex molecules showed that they were of approximately 1.7 megadaltons in size and were inserted within the ColE1 loop region of pMK1. However, inverted repeat structures were not seen in these two Cm transposons. Restriction enzyme cleavage analysis showed that both Tn3351 and Tn3352 were indistinguishable in their cleavage patterns, suggesting that they were almost identical in deoxyribonucleic acid sequence despite the difference in their origin. These results suggest that the reciprocal transposition of the Cmr gene might have occurred between Salmonella and E. coli in nature.
Fosfomycin kinetics after intravenous and oral administration to human volunteers
Authors: Goto M , Sugiyama M , Nakajima S , Yamashina H
Published: June 2012

The pharmacokinetics of fosfomycin, administered intravenously and orally at two different doses (20 and 40 mg/kg of body weight), was studied in seven volunteers. The elimination profile of this antibiotic, when administered intravenously, followed a two-compartment kinetic model, independent of dosage, giving an elimination half-life of 2.23 +/- 0.62 h and an average total volume of distribution at steady state of 0.34 liter/kg. Peak serum levels after rapid intravenous administration of 20 and 40 mg/kg were 132.1 +/- 31.8 and 259.3 +/- 32.5 micrograms/ml, respectively. Peak serum levels after oral administration were 7.1 +/- 1.6 and 9.4 +/- 3.6 micrograms/ml for the 20 and 40 mg/kg doses, respectively. During the first 24 h after administration, an average of 80% of the intravenous doses and less than 25% of the oral doses were recovered in the urine.