bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement by clofazimine and inhibition by dapsone of production of prostaglandin E2 by human polymorphonuclear leukocytes in vitro
Authors: Anderson R
Published: June 2012

The effects of the antileprosy agents clofazimine and dapsone (1 to 10 micrograms/ml) on the spontaneous and stimulated release of prostaglandin E2 (PG E2) by human polymorphonuclear leukocytes (PMNL) in vitro have been investigated. PMNL were obtained from normal adult volunteers and three patients with leprosy (two borderline lepromatous and one subpolar lepromatous leprosy). The synthetic chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) at a concentration of 10(-7) M was used as the stimulant of PG E2 synthesis. None of the test agents at the concentrations used inhibited the binding of radiolabeled FMLP to PMNL. However, dapsone at 5 and 10 micrograms/ml inhibited the spontaneous and FMLP-induced release of PG E2 by PMNL. Clofazimine, on the other hand, significantly increased both the spontaneous and the FMLP-induced synthesis of PG E2 by PMNL. The enhancing effects of clofazimine on FMLP-mediated synthesis of PG E2 were particularly striking and were observed at concentrations of 1 to 10 micrograms of the drug per ml. Measurements of PMNL spontaneous and FMLP-induced synthesis of PG E2 in the presence of both clofazimine and dapsone (5 micrograms/ml) indicated that the two drugs are mutually antagonistic. PMNL from both normal control subjects and patients with leprosy were equally sensitive to these effects of clofazimine and dapsone. The immunostimulatory and immunosuppressive properties of dapsone and clofazimine, respectively, may be related to the opposite effects of these agents on PG E2 synthesis in human leukocytes.
Pharmacokinetics of tobramycin and gentamicin in abusers of intravenous drugs
Authors: King C H , Creger R J , Ellner J J
Published: June 2012

The kinetics of aminoglycoside elimination were determined in 18 hospitalized narcotics abusers receiving gentamicin or tobramycin for treatment of severe infection. Rapid aminoglycoside elimination (requiring doses of greater than 5 mg/kg per day to maintain adequate drug levels) was noted in 12 of the 18 patients (18 of 27 clearance studies). Patients found to have rapid elimination were younger (P less than 0.01) and had larger drug distribution volumes (P less than 0.005), greater measured creatinine clearances (P less than 0.05), and lower creatinine levels in serum (P less than 0.001) than those with normal elimination. Nevertheless, by regression analysis, age, creatinine levels in serum, creatinine clearances, and drug distribution volumes proved to be unreliable predictors of individual aminoglycoside clearance. Measured drug half-life in serum appeared to be the only reliable predictor of drug clearance (r = 0.93). Patients with rapid drug elimination had aminoglycoside clearances 16 to 43% greater than measured creatinine clearances, suggesting an extraglomerular route of drug elimination. We conclude that in drug abuse patients a significant and clinically unpredictable interpatient variation occurs in aminoglycoside elimination and that accurate serum kinetics are needed to determine therapeutic dosing. In addicts younger than 35 years, with a creatinine level of less than 1.0 mg/100 ml in serum, the risk of inadequate therapy is high if standard dosing guidelines are followed. For this group, initial dosing of 8 mg/kg per day, with a drug half-life determination on the first dose, is recommended. Pharmacokinetic analysis is critical for all drug abusers treated with aminoglycosides for serious infection.
Multiclinic comparative study of norfloxacin and trimethoprim-sulfamethoxazole for treatment of urinary tract infections
Authors: Sabbaj J , Hoagland V L , Shih W J
Published: June 2012

Three hundred seventy patients with upper or lower urinary tract infections were entered into a multicenter, open comparative study. A total of 190 patients were treated with norfloxacin, and 180 patients were treated with trimethoprim-sulfamethoxazole. The percentage of strains susceptible to norfloxacin (99%) was significantly greater (P less than 0.001) than the percentage of strains susceptible to trimethoprim-sulfamethoxazole (90%). The percentages of patients with bacteriological outcomes of eradication were greater in the norfloxacin group (97%) than in the trimethoprim-sulfamethoxazole group (90%). The difference was significant (P less than 0.05). Seven patients (three treated with norfloxacin, four treated with trimethoprim-sulfamethoxazole) experienced early reinfection. Of 370 patients entered into the study, 20 patients experienced clinical adverse effects that were probably or definitely related to the study drug; 6 patients were in the group that received norfloxacin, and 14 were in the group that received trimethoprim-sulfamethoxazole. Study antimicrobial agents were discontinued because of clinical adverse effects in eight patients (norfloxacin, one patient; trimethoprim-sulfamethoxazole, seven patients). Three patients receiving norfloxacin and four patients receiving trimethoprim-sulfamethoxazole had laboratory adverse effects which were classified as probably or definitely drug related. None of the clinical or laboratory adverse effects was serious.
Comparison of moxalactam and cefazolin as prophylactic antibiotics during cesarean section
Authors: Rayburn W , Varner M , Galask R , Petzold C R , Piehl E
Published: June 2012

Prophylactic antibiotics have been shown to be effective in decreasing the incidence of febrile morbidity associated with cesarean section after labor. However, the relative effectiveness of different single antibiotics has been studied infrequently, and these investigations have been limited by small patient samples. Several new, broad-spectrum antibiotics are now available, and any further benefit from more traditional antibiotics for surgical prophylaxis remains untested. A randomized prospective double-blind therapeutic trial was therefore undertaken to compare the value of a first-generation cephalosporin (cefazolin) with a new third-generation cephalosporin (moxalactam). Between July 1981 and June 1983, 254 qualifying women who underwent primary cesarean section after labor were randomly chosen for either of the two treatment groups. Although not statistically significant, the rates of febrile morbidity, wound infection, and endometritis were less for those treated with cefazolin (4.0, 3.2, and 0.8%, respectively) than for those treated with moxalactam (9.2, 7.7, and 1.6%, respectively). No serious adverse effects were apparent in the mother and newborn infant from short-term exposure to either drug. Although the newer, more expensive, and broader-spectrum cephalosporin, moxalactam, was associated with a low postoperative febrile morbidity rate and short postpartum hospitalization, it was no more beneficial than cefazolin.
Pharmacokinetics of ciprofloxacin after oral and parenteral administration
Authors: Höffken G , Lode H , Prinzing C , Borner K , Koeppe P
Published: June 2012

In 12 fasting volunteers, the pharmacokinetics of ciprofloxacin (Bay o 9867; 1-cyclopropyl-6-fluor-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carbonic acid) were determined after the administration of 50, 100, and 750 mg orally as well as 50 and 100 mg intravenously over 15 min. Serum and urine concentrations were detected with a bioassay. In addition, urine concentrations after a 50-mg dosing were measured by high-pressure liquid chromatography. The serum course of ciprofloxacin could best be described by an open three-compartment model. High volumes of distribution (exceeding 200 liters/100 kg) suggested effective diffusions in the extravascular space. The terminal half-life of ciprofloxacin ranged between 3 and 4 h. High total and renal clearances suggested additional elimination pathways, such as tubular secretion, metabolism, or biliary excretion. After oral administration, absorption was sufficient, and the absolute bioavailability varied between 0.77 and 0.63. Maximal serum concentrations were attained 0.5 to 1 h after dosing; the higher dosage tended towards a delay in absorption. The proportion of the relative amount of metabolites to the total amount of drug excreted in urine increased from 29.7% after intravenous administration to 42.7% after oral dosing, indicating a first-pass effect of the liver. Ciprofloxacin concentrations with a bioassay were 3 to 27% higher than with high-pressure liquid chromatography, which may indicate the presence of biologically active metabolites. No side effects were recorded.
Comparative activity of ciprofloxacin against anaerobic bacteria
Authors: Sutter V L , Kwok Y Y , Bulkacz J
Published: June 2012

The in vitro activity of ciprofloxacin was assessed against 362 strains of anaerobic bacteria and compared with that of cefoxitin, clindamycin, metronidazole, and mezlocillin. Only 31% of the strains tested were susceptible to ciprofloxacin. The other agents were active against most of the strains tested.
Comparative in vitro activities of twelve antimicrobial agents against Campylobacter species
Authors: Fliegelman R M , Petrak R M , Goodman L J , Segreti J , Trenholme G M , Kaplan R L
Published: June 2012

The in vitro susceptibility of 27 Campylobacter jejuni, 31 Campylobacter coli, and 30 Campylobacter fetus subsp. fetus strains to 12 antimicrobial agents was determined. Ciprofloxacin, a new quinoline derivative, was the most active agent tested. Antimicrobial susceptibility differed among the three species tested.
Pharmacokinetics of imipenem-cilastatin in neonates
Authors: Freij B J , McCracken G H , Olsen K D , Threlkeld N
Published: June 2012

Imipenem and its renal dehydropeptidase I inhibitor, cilastatin, were coadministered intravenously in a 1:1 ratio to 30 newborns. Five infants each received single doses of 10, 15, or 20 mg/kg of both drugs. Concentrations in plasma were proportional to the administered dose, and cilastatin achieved consistently higher concentrations than did equivalent doses of imipenem because of its smaller volume of distribution. The pharmacokinetics of both drugs were best described by a one-compartment model. The plasma half-lives of imipenem were 1.7 to 2.4 h, whereas those of cilastatin were 3.9 to 6.3 h. The plasma clearance of cilastatin was approximately one-quarter of that of imipenem in the dose range tested. The urinary concentrations of imipenem were 50% of those of cilastatin despite its higher clearance from plasma. Fifteen additional newborns received five to eight doses of imipenem-cilastatin at 20 mg/kg per dose every 12 h. There was no accumulation of either drug in plasma after repeated administrations, and the mean concentrations in plasma were similar when measured on the first and last days of the multiple-dose study. There was marked intersubject variability, more so for cilastatin. The pharmacokinetics of both drugs in neonates resembled those observed in adults with moderate to severe renal insufficiency. Because the effects of enzyme inhibition on neonates are unknown, additional studies with imipenem-cilastatin (primaxin) are recommended.
Quantitative measurement of single- and double-strand breakage of DNA in Escherichia coli by the antitumor antibiotics bleomycin and talisomycin
Authors: Mirabelli C K , Huang C H , Fenwick R G , Crooke S T
Published: June 2012

We developed an assay in which single-strand breakage (ssb) and double-strand breakage (dsb) of intracellular DNA by chemical agents can be accurately quantitated and differentiated. Escherichia coli cells containing plasmid pBR322 DNA were incubated with the antitumor antibiotics bleomycin A2 (BLM A2) or talisomycin A (TLM A). The plasmid DNA was isolated and then analyzed by electrophoresis on 1% agarose gels to separate the following conformational forms of plasmid DNA: (i) native, covalently closed, super helical, form I; (ii) nicked, relaxed circular, form II; and (iii) double-strand broken, linear, form III. Quantitation by densitometric analysis of the gels showed that BLM A2 and TLM A were equally active in terms of the concentrations of drug necessary to reduce equivalent amounts of form I DNA in the cells, whereas in vitro (using isolated pBR322 DNA as a drug substrate) twofold more TLM A than BLM A2 was required to produce an equivalent amount of reduction in form I DNA. TLM A produced more intracellular dsb than did BLM A2. The intracellular dsb activities (dsb/ssb ratio) measured from BLM A2 and TLM A were equivalent to those measured for the respective agents when isolated pBR322 DNA was used as the substrate. In E. coli both ssb and dsb were repaired, but TLM A damage was repaired more slowly and to a lesser extent, which may reflect the relative frequency of dsb.
In vitro and in vivo activities of formycin B against Trypanosoma cruzi
Authors: McCabe R E , Remington J S , Araujo F G
Published: June 2012

The inosine analog formycin B was examined for in vitro and in vivo activities against Trypanosoma cruzi. concentration of formycin B as low as 0.1 microgram/ml markedly inhibited intracellular multiplication of T. cruzi strains both in macrophages and in L929 cells. Mice infected with 10(5) blood form trypomastigotes of the highly virulent strain Y of T. cruzi were completely protected against death by treatment with 11.8 or 5.9 mg of formycin B per kg administered intraperitoneally each day for 19 days. Four different strains of T. cruzi were used, and each was susceptible to formycin B administered either intraperitoneally or orally. Parasitological cure, however, was not achieved with any of the treatments used, including prolonged treatment for up to 10 weeks. Formycin B has a remarkable capacity for inhibiting the in vitro intracellular replication of T. cruzi and protecting mice against death due to the acute infection with the organism. It does not appear, however, to be able to completely eliminate T. cruzi from infected mice.
Determination of vancomycin in human serum by high-pressure liquid chromatography
Authors: Jehl F , Gallion C , Thierry R C , Monteil H
Published: June 2012

A rapid, accurate, reverse-phase high-pressure liquid chromatographic procedure for vancomycin quantitation in human serum, cerebrospinal fluid, and peritoneal fluid was developed. This procedure involves a simple chemical extraction of the antibiotic and is suitable for each of these body fluids. The column and mobile phase used provided a good resolution of the vancomycin peak with a retention time of 6.1 min. The precision of the assay was within the requirement for a daily routine clinical application. Coefficients of variation for within-day reproducibility were 5.80 and 6.28%, respectively, for samples at 50 and 25 micrograms/ml, and for between-day reproducibility they were 11.4 and 11.1%, respectively. No interference was found with respect to beta-lactam and aminoglycoside antibiotics and many other currently used drugs, indicating a good specificity for the procedure. The detection limit of 100 ng/ml has proven to be sufficient for monitoring drug levels in serum obtained after usual dosages. Drug levels in 112 clinical serum specimens assayed by high-pressure liquid chromatography were regressed against the levels obtained for the same samples by radioimmunoassay and fluorescent polarization immunoassay. Correlation coefficients were 0.945 and 0.967, respectively, and were highly significant (alpha less than 0.001).
Pharmacokinetics of imipenem and cilastatin in patients with cystic fibrosis
Authors: Reed M D , Stern R C , O'Brien C A , Yamashita T S , Myers C M , Blumer J L
Published: June 2012

The pharmacokinetics of imipenem, a new carbapenem antibiotic, and cilastatin, a metabolic inhibitor, were evaluated in 17 patients with cystic fibrosis. Imipenem and cilastatin were combined in a ratio of 1:1 in the infusion solution, and patients intravenously received 30, 60, or 90 mg of imipenem per kg of body weight per day, divided into four equal doses. Pharmacokinetic evaluation after the first dose and again under steady-state conditions revealed biodisposition characteristics which were similar and independent of the daily dose administered. Cilastatin concentrations in serum paralleled those of imipenem. A linear relationship between dose and area under the serum concentration-time curve for both compounds was observed, suggesting a first-order pharmacokinetic process. A total of 50 and 78% of the doses of imipenem and cilastatin, respectively, were recovered unchanged in the urine. The renal clearances of imipenem and cilastatin averaged 54 and 88%, respectively, of the serum clearance. These data suggest that an extrarenal mechanism may be involved in the overall elimination of imipenem. No patient experienced any clinical or biochemical abnormalities during drug therapy.
Biochemical properties of beta-lactamase produced by Flavobacterium odoratum
Authors: Sato K , Fujii T , Okamoto R , Inoue M , Mitsuhashi S
Published: June 2012

A constitutively produced beta-lactamase was purified from Flavobacterium odoratum GN14053. The purified enzyme gave a single protein band on polyacrylamide gel electrophoresis. The isoelectric point was 5.8, and the molecular weight was estimated to be about 26,000. The enzyme activity was inhibited by EDTA, iodine, p-chloromercuribenzoate, HgCl2, and CuSO4 but not by clavulanic acid, sulbactam, imipenem, and cephamycin derivatives. The enzyme showed a broad substrate profile, hydrolyzing oxyiminocephalosporins, cephamycins, imipenem, and some penicillins.
Comparative in vitro activity of sanguinarine against oral microbial isolates
Authors: Dzink J L , Socransky S S
Published: June 2012

MICs of sanguinarine were determined for 52 oral reference strains and 129 fresh isolates from human dental plaque. Sanguinarine was found to completely inhibit the growth of 98% of the isolates at a concentration of 16 micrograms/ml.
Inhibition of growth of Chlamydia trachomatis by nonoxynol-9 in vitro
Authors: Benes S , McCormack W M
Published: June 2012

We evaluated the ability of the widely used spermicide nonoxynol-9, Conceptrol gel containing nonoxynol-9, and Conceptrol vehicle (without nonoxynol-9) to inhibit the formation of inclusions of Chlamydia trachomatis in cycloheximide-treated McCoy cells. Conceptrol vehicle produced a non-dose-related 40 to 59% reduction of the number of inclusions formed. In contrast, the addition of nonoxynol-9 and Conceptrol gel containing nonoxynol-9 at a concentration of 100 micrograms/ml reduced the number of inclusions by 84 to 95%. Prolongation of contact between nonoxynol-9 and the chlamydial organisms from 90 to 180 min did not result in additional inhibition. Using a higher concentration of chlamydial organisms and diluting the drug-chlamydia mixture before inoculation of the monolayers, we were able to test higher concentrations of nonoxynol-9. At concentrations of 100 to 5,000 micrograms of nonoxynol-9 per ml, a dose-related 19 to 84% reduction of the number of inclusions was noted.
Antiherpes effects and pharmacokinetic properties of 9-(4-hydroxybutyl) guanine and the (R) and (S) enantiomers of 9-(3,4-dihydroxybutyl)guanine
Authors: Ericson A C , Larsson A , Aoki F Y , Yisak W A , Johansson N G , Oberg B , Datema R
Published: June 2012

Three acyclic guanosine analogs with similar structures, the (R) and (S) forms of 9-(3,4-dihydroxybutyl)guanine and 9-(4-hydroxybutyl)guanine, were compared for antiherpes activity in vivo and in vitro. The three guanosine analogs were viral thymidine kinase-dependent inhibitors of virus multiplication. In cell cultures, (S)-9-(3,4-dihydroxybutyl)guanine was the least active of these three drugs against a variety of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) strains. This was also the case for a certain HSV-1 or HSV-2 strain in different cell lines. In cell cultures, (R)-9-(3,4-dihydroxybutyl)guanine and 9-(4-hydroxybutyl)guanine had similar antiherpes activities. However, in vivo in cutaneous HSV-1 infections in guinea pigs treated topically and in systemic HSV-2 infections in mice treated orally or intraperitoneally, only (R)-9-(3,4-dihydroxybutyl)guanine had a therapeutic effect. The extremely short half-life in plasma and the high clearance of 9-(4-hydroxybutyl)guanine as compared with those of (R)-9-(3,4-dihydroxybutyl)guanine probably made 9-(4-hydroxybutyl)guanine inefficacious when given intraperitoneally or orally to mice infected with herpesvirus. On the other hand, no kinetic differences between (R)-9-(3,4-dihydroxybutyl)guanine and 9-(4-hydroxybutyl)guanine were observed in penetration through guinea pig skin ex vivo, and no preferential metabolism of 9-(4-hydroxybutyl)guanine in skin was noted. We deduced that high thymidine levels in guinea pig skin preferentially antagonize the antiviral effect of 9-(4-hydroxybutyl) guanine in cutaneous HSV-1 infections.
Metabolism and disposition of amifloxacin in laboratory animals
Authors: Johnson J A , Benziger D P
Published: June 2012

Sprague-Dawley rats received [14C]amifloxacin mesylate either orally or intravenously at 20 mg (base equivalent) per kg. Blood radioactivity peaked at 0.5 h after oral administration and was equivalent to 7.54 micrograms/ml for males and 6.73 micrograms/ml for females. After intravenous administration to rats, 52.5% of the dose was recovered in the urine of males and 45.3% in the urine of females within 72 h. The corresponding values after oral administration were 50.8% for males and 37.2% for females. The remainder of the dose was recovered in the feces. After intravenous administration of [14C]amifloxacin mesylate at 10 mg (base equivalent) per kg to female rhesus monkeys, 80.3% of the radioactivity was excreted in the urine at 24 h. The apparent first-order terminal elimination half-life of intact amifloxacin in plasma was 2.3 h; radioactivity in plasma was eliminated more slowly. Male rats excreted 26.2% of the dose in the urine as amifloxacin and 17.8% as the piperazinyl-N-oxide derivative of amifloxacin after intravenous administration. The corresponding amounts for female rats were 29.0% as amifloxacin and 7.8% as the piperazinyl-N-oxide metabolite. Similar excretion profiles were observed after oral administration. After intravenous administration, female monkeys excreted 54.5% of the dose in the urine as amifloxacin, 12.9% as the piperazinyl-N-desmethyl metabolite, and 5.6% as the piperazinyl-N-oxide during the first 12 h. In contrast, there was no evidence of the piperazinyl-N-desmethyl metabolite in rats.
In vitro activities of Ro 17-2301 and aztreonam compared with those of other new beta-lactam antibiotics against clinical isolates of Pseudomonas aeruginosa
Authors: Ng W W , Chau P Y , Leung Y K , Livermore D M
Published: June 2012

The in vitro activities of Ro 17-2301 and aztreonam against 191 Pseudomonas aeruginosa isolates were compared with those of five other beta-lactam antibiotics. Both compounds showed activities comparable to that of ceftazidime and were bactericidal. They were as effective against gentamicin-or carbenicillin-resistant isolates as against susceptible ones.
Amoxicillin-clavulanic acid in the treatment of lower respiratory tract infections caused by beta-lactamase-positive Haemophilus influenzae and Branhamella catarrhalis
Authors: Wallace R J , Steele L C , Brooks D L , Luman J I , Wilson R W , McLarty J W
Published: June 2012

Twenty-one adult patients hospitalized with lower respiratory tract infections due to Branhamella catarrhalis or Haemophilus influenzae or both were treated with the combination of oral amoxicillin and potassium clavulanate (Augmentin) in an open, noncomparative clinical trial. Diseases included pneumonia, empyema, and exacerbations of bronchiectasis and chronic lung disease. Thirteen of 16 B. catarrhalis and six of nine H. influenzae isolates were beta-lactamase positive. The patients with B. catarrhalis were treated for a mean of 5.3 days, and those with H. influenzae were treated for a mean of 7.0 days. The overall response to therapy was excellent, with 18 of 19 beta-lactamase-producing strains eradicated on therapy. One patient secondarily infected with Pseudomonas aeruginosa was a clinical failure, and two patients with H. influenzae who became culture positive again after therapy were considered microbiologic failures. Gastrointestinal side effects (especially nausea) were common, although all patients completed a course of therapy. Sputum levels of amoxicillin were surprisingly low (less than 0.05 to 0.54 micrograms/ml), a finding which may explain the high relapse rate (22%) seen with H. influenzae, as these are below the usual MICs of amoxicillin for this organism. The combination of amoxicillin plus potassium clavulanate appears to be an excellent drug for treatment of beta-lactamase-producing strains of these two species, although mild gastrointestinal side effects are common.
Biochemical mechanisms of the antileishmanial activity of sodium stibogluconate
Authors: Berman J D , Waddell D , Hanson B D
Published: June 2012

Pentavalent antimonial agents such as sodium stibogluconate (Pentostam; Burroughs Wellcome Co., London, United Kingdom) are the drugs of choice for the treatment of leishmaniasis, but their biochemical mechanisms of action are virtually unknown. The viability of Leishmania mexicana (WR 227) promastigotes and amastigotes was decreased 40 to 61% by a 4-h exposure to 500 micrograms of Sb (in the form of stibogluconate) per ml. Such exposure also resulted in a 51 to 65% decrease in incorporation of label into DNA, RNA, and protein; a 56 to 65% decrease in incorporation of label into purine nucleoside triphosphate; and a 34 to 60% increase in incorporation of label into purine nucleoside monophosphate and diphosphate. It is postulated that the apparent decrease in ATP and GTP synthesis from ADP and GDP contributes to decreased macromolecular synthesis and to decreased Leishmania viability. Further experiments suggested that inhibition of glycolysis and the citric acid cycle may partially explain the inability to phosphorylate ADP.
Inhibition of Chlamydia trachomatis growth in McCoy, HeLa, and human prostate cells by zinc
Authors: Greenberg S B , Harris D , Giles P , Martin R R , Wallace R J
Published: June 2012

Zinc salts (10(-4) and 10(-5) M) inhibited the number of Chlamydia trachomatis inclusions in McCoy, HeLa, and primary human prostate epithelial cell cultures. Addition of zinc salts 1 h before or 24 h after inoculation with C. trachomatis was found to inhibit growth. Both C. trachomatis serotype D and a lymphogranuloma venereum strain were inhibited by the zinc salts. Although the mechanism of inhibition is not known, the continued presence of the zinc appeared necessary for maximal effect. At the concentrations tested, zinc was not directly toxic to the McCoy cells. These results suggest that the levels of zinc in prostatic secretions may be sufficient to preclude the recovery of chlamydia in the diagnostic laboratory or to inhibit chlamydia from infecting the prostate in vivo.
Self-induced nystatin resistance in Dictyostelium discoideum
Authors: Kasbekar D P , Madigan S , Katz E R
Published: June 2012

The cellular slime mold Dictyostelium discoideum is normally susceptible to the action of the polyene antibiotic nystatin. We describe conditions under which transient nystatin resistance can be induced in the absence of detectable changes in sterol composition. These results suggest that nystatin plays a positive role in promoting resistance to itself.
Elimination of multicopy plasmid R6K by bleomycin
Authors: Attfield P V , Pinney R J
Published: June 2012

Bleomycin eliminated multicopy plasmid R6K from growing cells of Escherichia coli AB1157 but failed to cure either of the low-copy plasmids R1 or R46. Measurements of R6K-encoded beta-lactamase and of covalently closed plasmid DNA indicated that the drug causes a progressive reduction in plasmid copy number.
Effects of elevation of serum cholesterol and administration of amphotericin B complexed to lipoproteins on amphotericin B-induced toxicity in rabbits
Authors: Koldin M H , Kobayashi G S , Brajtburg J , Medoff G
Published: June 2012

Amphotericin B was infused into normal rabbits or rabbits made hypercholesterolemic by diet. There was no difference in amphotericin B-induced toxicity between these two groups. Amphotericin B given in a mixture with human low-density lipoproteins was more toxic than when given without lipoproteins.
Comparison of ceftazidime with cefamandole for therapy of community-acquired pneumonia
Authors: Engle J C , Lifland P W , Schleupner C J
Published: June 2012

Ceftazidime and cefamandole were compared in the treatment of pneumonia. The median MIC of ceftazidime for all Streptococcus pneumoniae (n = 17) and Haemophilus influenzae (n = 10) isolates was 0.125 microgram/ml. All other isolates were inhibited by less than 0.5 microgram of ceftazidime per ml, with the exception of a group B streptococcus (MIC = 4 micrograms/ml). Satisfactory clinical responses were observed in 91% (20 of 22) of cefamandole-treated patients and 85% (17 of 20) of ceftazidime-treated patients.
Specific inhibition of spermidine synthesis in Mycobacteria spp. by the dextro isomer of ethambutol
Authors: Paulin L G , Brander E E , Pösö H J
Published: June 2012

Only the dextro isomer of ethambutol inhibited mycobacterial spermidine synthase and spermidine biosynthesis. Inhibition of mycobacterial spermidine synthase appeared to be specific. Spermidine synthase from Mycobacterium fortuitum, which was resistant to ethambutol in vitro, required a higher concentration of ethambutol for its inhibition than the enzyme of susceptible Mycobacterium bovis.
Assessment of serum bactericidal activity after administration of cefoperazone, cefotaxime, ceftizoxime, and moxalactam to healthy subjects
Authors: Barriere S L , Ozasa D C , Mordenti J
Published: June 2012

Bactericidal activity in serum produced after administration of 1-g intravenous doses of cefoperazone, cefotaxime, ceftizoxime, and moxalactam was ascertained in six healthy subjects. The assay organisms were a strain of Staphylococcus aureus which was moderately susceptible to the drugs (MBC, 2 to 8 micrograms/ml) and an isolate of Escherichia coli which was highly susceptible (MBC, 0.08 to 0.3 microgram/ml). Drug concentrations and bactericidal titers were measured from samples taken for up to 12 h after the dose. No bactericidal activity against the S. aureus strain was found at 4 to 6 h and beyond for any of the drugs. Ranking of the in vivo bactericidal activity of the drugs was cefoperazone = cefotaxime greater than ceftizoxime = moxalactam. Against the E. coli isolate, bactericidal activity was present for 8 h for cefotaxime, and for 12 h for the other drugs. Ranking of the drugs in terms of extent and duration of in vivo bactericidal activity versus E. coli was moxalactam = ceftizoxime greater than cefoperazone greater than cefotaxime. After administration of 1-g doses of these new beta-lactams, bactericidal activity in serum was maintained for 12 h against highly susceptible bacteria. More frequent (6 to 8 h) or higher (greater than or equal to 2 g) dosing appears to be necessary to achieve prolonged serum bactericidal activity against less susceptible isolates (MBC, greater than or equal to 2 to 8 micrograms/ml).
Construction of a gentamicin resistance gene probe for epidemiological studies
Authors: Groot Obbink D J , Ritchie L J , Cameron F H , Mattick J S , Ackerman V P
Published: June 2012

A 7.7-kilobase BamHI fragment was cloned from the transconjugant of a clinical isolate of Escherichia coli containing a 120-kilobase multiresistance IncC plasmid. The recombinant plasmid conferred resistance to kanamycin, gentamicin, tobramycin, sulfamethoxazole, and trimethoprim. This clone was used to generate a series of subclones from which a 2.0-kilobase BamHI-HindIII probe containing a gentamicin 2''-O-adenylyltransferase [AAD(2'')] gene was obtained. This probe hybridized specifically in both colony and Southern hybridizations with the AAD(2'') gene but not with other resistance genes, including other aminoglycoside-modifying genes, or with a reference IncC plasmid lacking the AAD(2'') gene. The AAD(2'') gene may be part of a transposon, since hybridization occurred with both nonconjugative plasmids and the chromosome in some isolates.
Use of adjuvants for enhancement of rectal absorption of cefoxitin in humans
Authors: Davis S S , Burnham W R , Wilson P , O'Brien J
Published: June 2012

The biological availability of cefoxitin administered rectally in the form of suppositories was examined in six human subjects by a cross-over design. Four different suppository systems containing adjuvants expected to enhance the absorption of the drug were studied. The presence of sodium salicylate and a nonionic surface-active agent, Brij 35, gave increased bioavailability as high as 20% compared with 3% for a system without adjuvants. The quantity of sodium salicylate was found to have an influence on the quantity of cefoxitin absorbed, and the salicylate was absorbed over an extended period of time from the rectum. The suppositories were well tolerated, and there were no adverse effects on bowel flora.
Comparative single-dose pharmacokinetics of amantadine hydrochloride and rimantadine hydrochloride in young and elderly adults
Authors: Hayden F G , Minocha A , Spyker D A , Hoffman H E
Published: June 2012

The single-dose pharmacokinetics of amantadine hydrochloride and rimantadine hydrochloride were compared in a randomized, two-period, crossover study involving six young (less than or equal to 35 years) and six elderly (less than or equal to 60 years) adults. Subjects ingested single 200-mg oral doses after an overnight fast, and serial plasma (0 to 96 h), nasal mucus (0 to 8 h), and urine (0 to 24 h) samples were collected for assay of drug concentration by electron capture gas chromatography. For both groups combined, rimantadine differed significantly from amantadine in peak plasma concentration (mean +/- standard deviation, 0.25 +/- 0.06 versus 0.65 +/- 0.22 micrograms/ml), plasma elimination half-life (36.5 +/- 15 versus 16.7 +/- 7.7 h), and percentage of administered dose excreted unchanged in urine (0.6 +/- 0.8 versus 45.7 +/- 15.7%). No significant age-related differences were noted for rimantadine. Urinary excretion (0 to 24 h) of rimantadine and its hydroxylated metabolites averaged 19% of the administered dose. The maximum nasal mucus drug concentration was similar for both drugs (0.42 +/- 0.25 versus 0.45 +/- 0.32 micrograms/g), and the ratio of maximum nasal mucus to plasma concentration was over twofold higher after rimantadine than after amantadine. These findings may in part explain the clinical effectiveness of rimantadine in influenza A virus infections at dosages that have lower toxicity than those of amantadine.
Antimicrobial activity of ciprofloxacin against Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus determined by the killing curve method: antibiotic comparisons and synergistic interactions
Authors: Chalkley L J , Koornhof H J
Published: June 2012

A derivative of quinolinecarboxylic acid, ciprofloxacin (BAY o 9867) was found to be an effective bactericidal agent against Pseudomonas aeruginosa and Escherichia coli. A bactericidal effect was achieved immediately after the addition of ciprofloxacin. At a concentration of 0.5 micrograms/ml, culture viability was reduced from 5 X 10(5) to about 5 X 10(3) CFU/ml within 15 min, and at 0.1 micrograms/ml, a greater than 10-fold reduction in viability resulted during the first hour after exposure. This bactericidal activity observed during the lag phase in Mueller-Hinton broth was also demonstrated in a nongrowing system. The antibiotics used in comparative studies, i.e., tobramycin, aztreonam, cefotaxime, and azlocillin, did not show this initial bactericidal activity, and ciprofloxacin prevented culture regrowth at lower concentrations. Staphylococcus aureus was not as susceptible to ciprofloxacin; killing occurred at a concentration of 0.5 micrograms/ml only after the onset of exponential growth in the control culture. Synergistic interactions were observed with ciprofloxacin in combination with tobramycin and azlocillin against P. aeruginosa and with cefotaxime and tobramycin against E. coli.
In vitro antibacterial activity of SK&F 88070 against aerobic gram-positive and gram-negative cocci and Haemophilus influenzae
Authors: Gooch W M , Daly J A
Published: June 2012

The inhibitory activity of SK&F 88070, a cephalosporin whose kinetic characteristics in animals suggest the possibility of once-daily doses, was determined against 345 clinical isolates, and results were compared with the activities of ceftizoxime, ceftriaxone, moxalactam, methicillin, and ampicillin. The spectrum of SK&F 88070 is similar to that of ceftizoxime.
Antimicrobial susceptibility testing and phenotyping of Neisseria gonorrhoeae isolated from patients with ophthalmia neonatorum in Nairobi, Kenya
Authors: Brunham R C , Fransen L , Plummer F , Piot P , Slaney L , Bygdeman S , Nsanze H
Published: June 2012

Antimicrobial susceptibility testing, auxotyping-serotyping, and plasmid analysis were performed on 41 ocular isolates, 7 nasopharyngeal isolates, and 18 cervical isolates of Neisseria gonorrhoeae obtained during a recent treatment trial of gonococcal ophthalmia neonatorum in Nairobi, Kenya. Fourteen distinct serovar-auxotype patterns were observed with IB-1/Pro-strains which accounted for 59% of the isolates. Infection with multiple types of gonococci appeared to occur in 22% of the mothers since 4 of 18 paired maternal cervical and neonatal ocular isolates had mismatched serovar-auxotype patterns. Among 10 treatment failure isolates only 1 had a mismatched serovar-auxotype pattern. Six (15%) of the ocular isolates were penicillinase-producing N. gonorrhoeae (PPNG). Five had the 4.4-megadalton (Md) beta-lactamase plasmid and one had the 3.2-Md beta-lactamase plasmid. The 24.5-Md plasmid was found in 5 of 6 PPNG strains and in 8 of 35 non-PPNG strains (P less than 0.02). For most antimicrobial agents, PPNG and non-PPNG strains showed similar patterns of susceptibility. Ceftriaxone was the most active of the antibiotics tested, with all strains having an MIC less than or equal to 0.06 mg/liter. Among non-PPNG strains, 15 (43%) had a penicillin MIC greater than or equal to 2 mg/liter and were considered intrinsically resistant to penicillin. Overall, non-PPNG intrinsically resistant strains had greater resistance to other antibiotics than did non-intrinsically resistant strains (P less than or equal to 0.006). The Mtr phenotype was found in 53% of these strains.
Plasmid-mediated resistance to lincomycin by inactivation in Staphylococcus haemolyticus
Authors: Leclercq R , Carlier C , Duval J , Courvalin P
Published: June 2012

Staphylococcus haemolyticus BM4610 was resistant to high levels of lincomycin and susceptible to macrolides, clindamycin, and streptogramins. This resistance phenotype, not previously reported for a human clinical isolate, was due to inactivation of the antibiotic. The gene conferring resistance to lincomycin in strain BM4610 was carried by a 2.5-kilobase plasmid, pIP855, which was cloned in Escherichia coli. Plasmid pIP855 caused inactivation of both lincomycin and clindamycin in S. haemolyticus and in E. coli but conferred detectable resistance to lincomycin only in S. haemolyticus and to clindamycin only in E. coli.
Comparative in vitro activities of MDL 473, rifampin, and ansamycin against Mycobacterium intracellulare
Authors: Cynamon M H
Published: June 2012

The susceptibilities of 20 clinical isolates of Mycobacterium intracellulare to rifampin, MDL 473, and ansamycin were determined by broth and agar dilution methods. Ansamycin was more active than MDL 473, which in turn was usually more active than rifampin by either method. The MICs for 90% of the strains tested by agar dilution were 1, 2, and 4 micrograms of ansamycin, MDL 473, and rifampin per ml, respectively.
Reversal of the in vitro susceptibility of enterococci to trimethoprim-sulfamethoxazole by folinic acid
Authors: Zervos M J , Schaberg D R
Published: June 2012

The in vitro susceptibilities of 21 clinical isolates of Streptococcus faecalis to trimethoprim (TMP) in combination with sulfamethoxazole (SMX) was evaluated in Mueller-Hinton broth (MHB) in the presence and absence of folinic acid as well as in urine. The mean MIC and MBC in MHB, expressed as the TMP concentration, was 0.13 and 0.32 micrograms of TMP-SMX per ml, respectively. In MHB supplemented with folinic acid, the mean MIC and MBC was 3.3 and 5.5 micrograms of TMP-SMX per ml, respectively. In urine the mean MIC of TMP-SMX for these isolates was 8.1 micrograms/ml (range, 1.6 to 50 micrograms/ml). All isolates were inhibited by less than 0.01 micrograms of TMP-SMX per ml when methotrexate was added to the urine.
In vitro activity of Ro 15-8074, a new oral cephalosporin, against Neisseria gonorrhoeae
Authors: Ng W S , Chau P Y , Leung Y K , Wong P C
Published: June 2012

Ro 15-8074, a new cephalosporin the pivaloyloxymethylester of which (Ro 15-8075) is orally absorbable, showed greater in vitro activity than cefaclor against 48 Neisseria gonorrhoeae strains, including 25 penicillinase-producing strains. Unlike cefaclor, Ro 15-8074 was unaffected by increase in inoculum size, and it exhibited a remarkable stability against gonococcal beta-lactamase hydrolysis.
Pharmacokinetics and bactericidal activity of cefuroxime axetil
Authors: Ginsburg C M , McCracken G H , Petruska M , Olson K
Published: June 2012

The pharmacokinetics of cefuroxime axetil were studied in 10 adult volunteers aged 24 to 31 years (mean age, 27), 22 infants and children aged 11 to 68 months (mean age, 33 months), and 11 children aged 7 years, 7 months to 12 years, 3 months (mean age, 11 years, 1 month). Mean peak plasma concentrations of cefuroxime occurred between 90 and 120 min in all study patients and were independent of the fasting or feeding status. The areas under the concentration-time curves were significantly higher in adult volunteers who received cefuroxime axetil with milk than in those who received the drug while fasting or with applesauce. The bioavailability of cefuroxime axetil was significantly enhanced in children by the concomitant ingestion of cefuroxime axetil and infant formula or whole milk. The areas under the concentration-time curves were 25 to 88% higher when cefuroxime axetil and milk were administered simultaneously than when the same dose was given to all fasting patients. The plasma bactericidal activities of cefuroxime against beta-lactamase-positive and -negative strains of Haemophilus influenzae and Staphylococcus aureus at the time of peak plasma concentrations were independent of feeding status and were similar in adults and in children. Against these strains, 52% of the children and 38% of the adults had peak bactericidal levels of 1:8 or greater.
Clinical efficacy and safety of cefmenoxime in children
Authors: Tansino G F , Hammerschlag M R , Congeni B L , Cox P A , Doraiswamy B , duBouchet L
Published: June 2012

Cefmenoxime, an investigational semisynthetic cephalosporin, was evaluated in 18 pediatric patients with a variety of infections. There were seven patients with urinary tract infections, two with wound infections, two with osteomyelitis, two with abscess infections, one with cervical adenitis, one with hidradenitis, one with pneumonia and sepsis, one with periorbital cellulitis, and one with ventriculitis. A total of 16 (88%) patients had a satisfactory clinical response demonstrated by improvement in clinical signs and symptoms. A total of 12 (67%) patients demonstrated eradication of their infecting organisms. Of the pathogens isolated in these patients, 16 isolates were susceptible to cefmenoxime. One patient developed a generalized urticarial rash that resolved within 24 h after cessation of cefmenoxime therapy. Mean peak level in serum after intravenous infusion was 55 micrograms/ml.
Prophylaxis of murine candidiasis via application of liposome-encapsulated amphotericin B and a muramyl dipeptide analog, alone and in combination
Authors: Mehta R T , Lopez-Berestein G , Hopfer R L , Mehta K , White R A , Juliano R L
Published: June 2012

The present study was conducted to examine the effect of a lipophilic analog of muramyl dipeptide, 6-O-stearoyl-N-acetylmuramyl-L-alpha-aminobutyryl-D-isoglutamine (6-O-S-Abu-MDP), a macrophage activator, on the prophylactic activity of liposomal amphotericin B (L-AmpB) against disseminated candidiasis in mice. Multilamellar vesicles containing AmpB and (6-O-S-Abu)-MDP were prepared by using dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol (7:3 molar ratio). Hale-Stoner mice (6 to 8 weeks old) were injected with 7 X 10(5) CFU of Candida albicans 336 isolated from a patient. Groups of mice were injected intravenously with different doses of L-AmpB and L-(6-O-S-Abu)-MDP, individually or in combination, 2 days before challenge with C. albicans. The mice were injected with a fixed dose of L-AmpB (1.2 mg/kg in 400 mg of lipid per kg) and various doses of L-(6-O-S-Abu)-MDP (0.6, 1.2, 2, and 4 mg/kg in 400 mg of lipid per kg) or vice versa. Other control groups included untreated mice and those receiving empty liposomes (400 mg of lipid per kg), free AmpB (0.6 mg/kg), or free (6-O-S-Abu)-MDP (4 mg/kg). The mice receiving L-AmpB (1.2 mg/kg) plus L-(6-O-S-Abu)-MDP (0.6 to 4.0 mg/kg) survived up to 25 to 30 days as compared with those injected with L-AmpB alone (15 days) or with L-(6-O-S-Abu)-MDP alone (10 to 15 days). All the mice in other control groups died within 7 to 11 days. The kidney cultures of the mice that received L-AmpB (4 mg/kg) plus L-(6-O-S-Abu)-MDP (1.2 mg/kg) were free of C. albicans infection, unlike those injected with L-AmpB. Variance analysis of these findings indicates a synergistic activity between L-AmpB and L-(6-O-S-Abu)-MDP in the prophylaxis of candidiasis.
Rapid method for determination of kanamycin and dibekacin in serum by use of high-pressure liquid chromatography
Authors: Kubo H , Kobayashi Y , Nishikawa T
Published: June 2012

A rapid, simple, and accurate method for the determination of kanamycin and dibekacin in serum by use of high-pressure liquid chromatography is described. The serum proteins were precipitated with 3.5% perchloric acid containing sodium octanesulfonate. After centrifugation, a sample of the supernatant was directly injected into the chromatograph. The determination of kanamycin and dibekacin was performed by a combination of reverse-phase, ion-pair chromatography, postcolumn derivatization with o-phthalaldehyde, and fluorescence detection. The correlation coefficients with fluorescence polarization immunoassay were 0.996 for kanamycin and 0.957 for dibekacin.
Determination of ansamycin MICs for Mycobacterium avium complex in liquid medium by radiometric and conventional methods
Authors: Heifets L B , Iseman M D , Lindholm-Levy P J , Kanes W
Published: June 2012

A radiometric method to determine the MIC of ansamycin (LM427) for Mycobacterium avium complex clinical isolates has been developed. It is based on a comparison of the conventional growth curve determination and the radiometric detection of growth (growth index) in the same liquid medium (7H12 broth). This new method requires less time and labor than does a conventional determination of MIC in liquid medium (CFU). Other advantages of this method include relatively short periods of exposure of the drug to 37 degrees C and the composition of 7H12 broth, which has practically no substrates which could absorb or bind the drug. Thus, a more accurate estimation of the MIC in this medium can be expected than by the conventional agar dilution (proportion) method. The MICs of ansamycin appeared to be higher in agar plates than in 7H12 broth. More than 70% of the isolates had a broth-determined MIC one to three times lower than the average peak concentration of ansamycin achieved in sera of patients. The wide range of MICs suggests the importance of testing susceptibility in broth with many concentrations in addition to, or rather than in, agar plates with concentrations of 2.0 or 1.0 micrograms/ml only. Taking into account relatively low levels of ansamycin in sera of patients, it would be appropriate to compare the MICs with the levels in serum to make the outcome of chemotherapy more predictable.