bluuebunny/crossref_metadata_2025 huggingface dataset:
Concentrations of ofloxacin in serum and cerebrospinal fluid of patients without meningitis receiving the drug intravenously and orally
Authors: Bitar N , Claes R , Van der Auwera P
Published: June 2012

The cerebrospinal fluid (CSF) penetration of ofloxacin given orally or or intravenously was studied in cancer patients without meningitis. Each patient was assigned to a different sampling time to assess the relation between time and penetration. Ofloxacin was measured in serum and CSF by high-pressure liquid chromatography and bioassay. In addition, the bactericidal titers were measured in CSF and serum against a set of relevant bacteria. Concentrations measured by high-pressure liquid chromatography and bioassay were well correlated. Peak concentrations in CSF (0.4 to 1 microgram/ml) were observed 2 to 4 h after infusion or oral administration. Peak concentrations in serum were observed just after infusion (2 to 3.5 micrograms/ml) or 1 to 2 h after oral administration (1.7 to 4 micrograms/ml). Measured bactericidal titers were well correlated with the titers expected from the MBC and concentration. High CSF bactericidal titers were observed against Neisseria meningitidis, Haemophilus influenzae, and Escherichia coli, whereas low or no bactericidal titers were obtained against Staphylococcus aureus, Listeria monocytogenes, and Streptococcus pneumoniae.
Evaluation of difloxacin in the treatment of uncomplicated urethral gonorrhea in men
Authors: Smith B L , Cummings M , Benes S , Draft K , McCormack W M
Published: June 2012

Difloxacin is a new quinolone antimicrobial agent with in vitro activity against both Neisseria gonorrhoeae and Chlamydia trachomatis and a long (26-h) half-life. A single oral dose of 200 mg of difloxacin was used to treat 30 men with uncomplicated urethral gonorrhea in an open trial. Of the isolates of N. gonorrhoeae, three produced penicillinase and two were resistant to tetracycline. N. gonorrhoeae was eradicated from all 29 evaluable patients. The geometric mean MIC of difloxacin for 30 pretreatment N. gonorrhoeae isolates was 0.014 (range, less than or equal to 0.0039 to 0.03) microgram/ml. Four (13.3%) of the 30 subjects with gonococcal urethritis also had C. trachomatis recovered from their pretreatment cultures. Treatment with difloxacin was associated with the eradication of C. trachomatis from all four men. In addition, C. trachomatis was isolated from the posttreatment culture of only one man who had a negative culture before treatment. Nineteen patients (65.5%) reported adverse experiences, and 17 of them (58.6%) developed symptoms suggestive of central nervous system dysfunction. An oral dose of 200 mg of difloxacin is effective treatment for uncomplicated urethral gonorrhea and may also eliminate a coexisting infection with C. trachomatis. Side effects may limit the utility of this agent.
Combination effect of recombinant human interleukin-1 alpha with antimicrobial agents
Authors: Nakamura S , Minami A , Fujimoto K , Kojima T
Published: June 2012

Combination effects of recombinant human interleukin-1 alpha with ceftazidime, moxalactam, gentamicin, enoxacin, amphotericin B, miconazole, or an immunoglobulin preparation were evaluated in systemic infections with Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans in normal mice and systemic infection with P. aeruginosa in mice with leukopenia induced by preadministration of cyclophosphamide. Synergistic effects were generally observed at interleukin-1 alpha doses as low as 1 to 30 ng per mouse with most combinations. The results show the possibility that recombinant human interleukin-1 alpha could be of help for treating obstinate infections not successfully treated with antimicrobial agents alone.
Treatment of experimental disseminated candidiasis with cilofungin
Authors: Perfect J R , Hobbs M M , Wright K A , Durack D T
Published: June 2012

The efficacy of cilofungin treatment of experimental disseminated candidiasis in rabbits was examined. Cilofungin treatment reduced yeast counts, especially in the kidney, with activity comparable to that of amphotericin B. The peak level of cilofungin in serum was measured at 5 min after administration of a single dose, with no drug detectable after 90 min.
9-(2-Phosphonylmethoxyethyl)adenine in the treatment of murine acquired immunodeficiency disease and opportunistic herpes simplex virus infections
Authors: Gangemi J D , Cozens R M , De Clercq E , Balzarini J , Hochkeppel H K
Published: June 2012

The murine model of acquired immunodeficiency disease was used to evaluate both the antiretroviral and antiherpetic activities of the acyclic nucleotide analog 9-(2-phosphonylmethoxyethyl)adenine (PMEA). The antiretroviral activity of PMEA was compared with that of azidothymidine (AZT) in mice receiving the drug either immediately after infection or at late times in disease progression. Both AZT (oral, 30 mg/kg) and PMEA (parenteral, 25 and 5 mg/kg) were effective in slowing the development of disease when administered daily beginning on the day of infection. In contrast, neither drug alone was effective in modifying disease outcome when administered several weeks after viral infection. Human recombinant alpha interferon (rhuIFN alpha-B/D at 5 x 10(7) U/kg) was also ineffective when administered late in the course of disease. However, when administered in combination, both alpha interferon and PMEA (25 mg/kg) were able to suppress disease progression even when treatment was initiated as late as 3 weeks postinfection. Mice that were immunocompromised due to LP-BM5 virus infection were highly susceptible to acute (lethal) infection with herpes simplex virus type 1, whereas their immunocompetent littermates were not. PMEA was as effective as acyclovir in the treatment of opportunistic herpes simplex virus type 1 infections in LP-BM5 virus-infected mice. Thus, like AZT, PMEA was effective against retrovirus infection, and, like acyclovir, PMEA was effective against herpes simplex virus type 1 infection. This gives PMEA the unique potential of being useful in the treatment of opportunistic herpes simplex virus infections as well as the underlying retroviral disease.
Influence of ranitidine, pirenzepine, and aluminum magnesium hydroxide on the bioavailability of various antibiotics, including amoxicillin, cephalexin, doxycycline, and amoxicillin-clavulanic acid
Authors: Deppermann K M , Lode H , Höffken G , Tschink G , Kalz C , Koeppe P
Published: June 2012

Two randomized double-blind crossover studies and one randomized crossover study were performed to document possible drug-drug interactions between antacids (aluminum magnesium hydroxide, 10 ml per dose for 10 doses), antimuscarinic drugs (pirenzepine, 50 mg per dose for 4 doses), and H2-blockers (ranitidine, 150 mg per dose for 3 doses) and amoxicillin (1,000 mg), cephalexin (1,000 mg), doxycycline (200 mg), and amoxicillin-clavulanic acid (625 mg). Ten healthy volunteers participated in each study. Concentrations in serum and urine were measured by bioassay, and pharmacokinetic parameters were calculated by the usual open one- or two-compartment models (statistics were determined by the Wilcoxon test). The antacid, pirenzepine, and ranitidine had no influence on the bioavailability of amoxicillin, cephalexin, and amoxicillin-clavulanic acid. Only small differences could be observed in the pharmacokinetic parameters, but they are not of therapeutic importance. However, the antacid caused a significant (P less than 0.01) reduction in the gastrointestinal absorption of doxycycline (area under the concentration-time curve, 38.6 +/- 22.7 mg.h/liter, fasting; 6.0 +/- 3.2 mg.h/liter, with antacid), resulting in subtherapeutic levels of doxycycline.
Toxicity and efficacy of 2',3'-dideoxycytidine in clinical trials of pigtailed macaques infected with simian retrovirus type 2
Authors: Tsai C C , Follis K E , Yarnall M , Blakley G A
Published: June 2012

Four dosing regimens of 2',3'-dideoxycytidine (ddC) were administered intravenously for 10 to 28 days to 18 pigtailed macaques with simian acquired immunodeficiency syndrome. Ten macaques naturally infected with simian acquired immunodeficiency syndrome retrovirus serotype 2 (SRV-2), the etiologic agent of simian acquired immunodeficiency syndrome, received ddC by continuous intravenous infusion or by a daily bolus injection for 10 to 12 days. Another eight macaques that were negative for SRV-2 and antibody received ddC prophylaxis prior to challenge with virus and continued to receive ddC therapy for up to 28 days postchallenge. All monkeys treated with a continuous intravenous dose of ddC, which maintained plasma concentrations of ddC at levels known to inhibit SRV-2 in vitro, developed dose-related toxic effects, including leukopenia, anemia, lethargy, and decreased appetite. Monkeys treated with a daily bolus injection of ddC experienced more severe toxic effects than those on the continuous intravenous regimen, including exfoliative dermatitis and peripheral neuropathy. At the concentrations of ddC administered, no significant inhibition of SRV-2 replication was detected in naturally infected macaques. However, a prophylactic regimen of ddC did have an inhibitory effect on SRV-2. Our findings suggest that ddC may be valuable as a short-term prophylactic treatment rather than as a long-term therapy.
Multiplicity of TEM-derived beta-lactamases from Klebsiella pneumoniae strains isolated at the same hospital and relationships between the responsible plasmids
Authors: Chanal C M , Sirot D L , Petit A , Labia R , Morand A , Sirot J L , Cluzel R A
Published: June 2012

Five plasmid-mediated beta-lactamases conferring high-level resistance to ceftazidime were isolated from Klebsiella pneumoniae strains in the same hospital. These enzymes had isoelectric points ranging from 5.3 to 6.5 (CAZ-1, 5.55; CAZ-2, 6.0; CAZ-3, 5.3; CAZ-6, 6.5; and CAZ-7, 6.3). All isolates and their Escherichia coli transconjugants were highly resistant to amoxicillin (MICs, greater than 4,096 micrograms/ml), piperacillin (64 to 256 micrograms/ml), cephalothin (32 to 256 micrograms/ml), and ceftazidime (32 to 512 micrograms/ml) but remained moderately susceptible to cefotaxime (0.5 to 8 micrograms/ml). Only CAZ-6- and CAZ-7-producing strains were highly resistant to aztreonam (64 to 128 micrograms/ml). All the isolates remained susceptible to moxalactam and imipenem. The reduced activity of piperacillin, cefotaxime, ceftazidime, or aztreonam was restored by 2 micrograms of clavulanate, sulbactam, tazobactam, or brobactam per ml for E. coli producing CAZ-2, CAZ-3, and CAZ-7. Sulbactam had a lower protective effect than other inhibitors for E. coli harboring CAZ-1 and especially CAZ-6. Except for CAZ-1, which was mediated by a 150-kilobase (kb) plasmid (pCFF14), the other ceftazidimases were mediated by plasmids of 85 kb with EcoRI digestion patterns similar to that of pCFF04 encoding CTX-1 beta-lactamase. A TEM probe hybridized with a 19-kb EcoRI fragment of all these closely related plasmids.
Combined antibody and ganciclovir treatment of murine cytomegalovirus-infected normal and immunosuppressed BALB/c mice
Authors: Rubin R H , Lynch P , Pasternack M S , Schoenfeld D , Medearis D N
Published: June 2012

The efficacy of treatment with ganciclovir (DHPG) and antibody activity-containing ascitic fluid (AF) separately and in combination was studied in normal and immunosuppressed BALB/c mice challenged intraperitoneally with a lethal dose (10(6) PFU) of murine cytomegalovirus (CMV). With combination therapy, lower doses of both DHPG and AF were often as effective as a higher dose of either agent given singly. For instance, the survival rate of murine CMV-challenged immunosuppressed mice was doubled when 4 mg of DHPG per kg and a 1:16 dilution of AF were both administered in contrast to when each was used alone. In both groups of animals, combination therapy was shown to be more effective than either therapy individually, even when initiation of therapy was delayed as long as 48 h. Such an approach holds promise for decreasing the expense associated with antibody use and the dose-related toxicity associated with DHPG use while maintaining or possibly increasing the efficacy of prophylaxis and therapy of serious CMV disease in humans.
Influence of an antacid containing aluminum and magnesium on the pharmacokinetics of cefixime
Authors: Healy D P , Sahai J V , Sterling L P , Racht E M
Published: June 2012

Interaction studies in dogs have indicated that antacids significantly decrease the oral bioavailability of cefixime. Twelve healthy adult male volunteers participated in a randomized, four-way crossover trial to evaluate the influence of an aluminum-magnesium antacid (Maalox; 20 ml) on the pharmacokinetics of cefixime (400 mg). Regimens were (i) cefixime alone; (ii) cefixime simultaneous with antacid; (iii) cefixime 2 h before antacid; and (iv) cefixime 2 h after antacid. Serial blood and urine samples were collected over a 24-h period following each dose of cefixime. There was a 1-week washout interval between regimens. Cefixime concentrations in serum and urine were analyzed by high-performance liquid chromatography. Maximum cefixime concentrations in serum for regimens i through iv were (mean +/- standard deviation) 4.9 +/- 1.4, 5.7 +/- 1.3, 5.1 +/- 1.0, and 5.5 +/- 1.5 micrograms/ml, respectively. Corresponding values for area under the serum concentration-time curve extrapolated to infinity were 38.3 +/- 14.5, 42.8 +/- 13.9, 38.5 +/- 9.8, and 41.6 +/- 16.7 micrograms.h/ml. There was a trend toward increased concentrations in serum and area under the curve of cefixime when it was administered concomitantly with antacid; however, these differences were not statistically significant (P greater than 0.05; analysis of variance). We conclude that single-dose administration of an aluminum-magnesium antacid does not significantly decrease the oral bioavailability of cefixime.
In vitro susceptibilities of oral bacterial isolates to spiramycin
Authors: Chan E C , al-Joburi W , Cheng S L , Delorme F
Published: June 2012

Four hundred strains of oral bacteria were tested for their susceptibility to spiramycin. Actinobacillus actinomycetemcomitans and most species of Lactobacillus were resistant to the antibiotic. All strains of cariogenic Streptococcus mutans and most strains of bacterial species implicated in adult chronic periodontitis (Bacteroides gingivalis, B. intermedius, and Treponema denticola) were susceptible to spiramycin.
Azidothymidine triphosphate is an inhibitor of both human immunodeficiency virus type 1 reverse transcriptase and DNA polymerase gamma
Authors: König H , Behr E , Löwer J , Kurth R
Published: June 2012

The reverse transcriptase from human immunodeficiency virus type 1 was purified from the virus to near homogeneity. The enzyme was shown to possess both RNA-dependent and DNA-dependent DNA-synthesizing activity. Activated DNA as a heteropolymeric substrate was used as efficiently as was the homopolymeric substrate poly(rA)-oligo(dT). The Michaelis-Menten constants were determined for each of the four nucleotides needed to elongate a natural template primer. Azidothymidine triphosphate, a well-known inhibitor of the enzyme, inhibited the enzyme competitively with respect to dTTP and noncompetitively with respect to the other nucleotides. Azidothymidine triphosphate acted as an efficient inhibitor of cellular DNA polymerase gamma, whereas other enzymes of eucaryotic DNA metabolism, namely, DNA polymerase alpha-primase and DNA polymerase beta, were not inhibited. This finding may explain why some acquired immunodeficiency syndrome patients suffer side effects during azidothymidine therapy.
Comparative in vitro activities of pristinamycin and other antimicrobial agents against genital pathogens
Authors: Lefevre J C , Bauriaud R
Published: June 2012

The MICs of pristinamycin for genital pathogens were compared with those of ampicillin, tetracycline, erythromycin, and ciprofloxacin. Pristinamycin was active against all the strains studied. Because of this activity and its lack of toxicity, pristinamycin might be a valuable therapeutic agent for treating major sexually transmitted diseases.
Interaction of E1040 with cephalosporinase from Citrobacter freundii GN7391
Authors: Inoue E , Mitsuhashi S
Published: June 2012

The interactions of E1040 with cephalosporinase from Citrobacter freundii, including affinity and hydrolysis, were studied in comparison with those of cefotaxime and ceftazidime. E1040 showed a higher stability at low drug concentrations and a much lower affinity for the enzyme than did cefotaxime or ceftazidime. These enzymological properties explain the high activity of E1040 against cephalosporinase-producing C. freundii.
Mode of action of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL 39123) against herpes simplex virus in MRC-5 cells
Authors: Hodge R A , Perkins R M
Published: June 2012

The metabolism and mode of action of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL 39123) were studied in herpes simplex virus type 1 (HSV-1)-infected and uninfected MRC-5 cells and compared with those of acyclovir. In uninfected cells incubated with 10 microM acyclonucleoside for 4 h, no phosphorylation of either BRL 39123 or acyclovir was detected. In contrast, in HSV-1-infected cells, both BRL 39123 and acyclovir were phosphorylated up to the triphosphate esters. Phosphorylation of BRL 39123 occurred much more rapidly and proceeded to a greater extent than did that of acyclovir. Furthermore, following the removal of acyclonucleoside from the culture medium, the intracellular triphosphate ester of BRL 39123 was much more stable than was that of acyclovir, the half-lives being about 10 and 0.7 h, respectively. BRL 39123 treatment effectively inhibited the formation of HSV-1 DNA in infected MRC-5 cells, 50% inhibitory concentrations of BRL 39123 and acyclovir being 0.04 microgram/ml (0.16 microM) and 0.15 microgram/ml (0.67 microM), respectively. In addition, BRL 39123 was shown to be more effective than acyclovir at inhibiting viral DNA synthesis following short treatment times, presumably reflecting the greater stability of BRL 39123 triphosphate. Neither BRL 39123 nor acyclovir inhibited cellular DNA synthesis in uninfected cells at concentrations of up to 100 micrograms/ml.
Effects of elfamycins on elongation factor Tu from Escherichia coli and Staphylococcus aureus
Authors: Hall C C , Watkins J D , Georgopapadakou N H
Published: June 2012

Six kirromycin analogs (elfamycins) were compared on the basis of their inhibition of Escherichia coli poly(U)-directed poly(Phe) synthesis and stimulation of elongation factor Tu (EF-Tu)-associated GTPase activity. The elfamycins tested were kirromycin, aurodox, efrotomycin, phenelfamycin A, unphenelfamycin, and L-681,217. The last three lack the pyridone ring present in the other elfamycins. All the elfamycins inhibited poly(U)-dependent poly(Phe) synthesis and stimulated EF-Tu-associated GTPase activity, suggesting that the pyridone ring is not essential for activity. The six elfamycins were also examined in a poly(U)-directed, poly(Phe)-synthesizing system derived from Staphylococcus aureus and had 50% inhibitory concentrations of greater than or equal to 1 mM. When S. aureus ribosomes and E. coli elongation factors were combined in a hybrid poly(Phe)-synthesizing system, aurodox produced essentially complete inhibition of poly(Phe) synthesis with a 50% inhibitory concentration of 0.13 microM. This suggests that the observed high MICs of kirromycin and its congeners in S. aureus reflect a kirromycin-resistant EF-Tu rather than permeability constraints.
Characterization of a halothane-resistant strain of measles virus
Authors: Bedows E , Davidson B A , Williams B A , Knight P R
Published: June 2012

A strain of measles virus (MVr) whose replication demonstrated increased resistance to halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) exposure compared with the susceptible parental strain (MVs) is described. After exposure to a 1.2% halothane concentration, substantial amounts of the measles virus H protein were detected in MVr-infected Vero cell lysates by immunoprecipitation and polyacrylamide gel electrophoresis or by quantitative immunofluorescence staining. The protein was barely detectable in identically treated MVs-infected lysates, however. The recovery of all other measles virus proteins studied was the same in MVr- and MVs-infected cells at this anesthetic concentration. Thus, the altered expression of a single gene product appears to be responsible for the observed halothane resistance.
Therapeutic efficacy of liposome-entrapped rifampin against Mycobacterium avium complex infection induced in mice
Authors: Saito H , Tomioka H
Published: June 2012

Liposome-entrapped rifampin (RFP) was examined for therapeutic efficacy against experimental infection induced in mice by the Mycobacterium avium complex. Intraperitoneal injections (once daily, six times weekly) of liposome-entrapped RFP led to a greater reduction in bacterial growth in the lungs and spleen of infected mice than did free RFP alone. Liposome-entrapped RFP given to mice via the intramuscular or subcutaneous route failed to show such an increased therapeutic efficacy. RFP entrapped in the lipid layer of liposomal vesicles exhibited a level of therapeutic activity similar to that seen with RFP encapsulated in the inner solute of the vesicles. Entrapment of RFP in liposomal vesicles increased incorporation of the drug into host peritoneal macrophages and increased the activity of the agent against M. avium complex phagocytosed into the macrophages.
Genetic basis of antibiotic resistance in Aerococcus viridans
Authors: Buu-Hoï A , Le Bouguénec C , Horaud T
Published: June 2012

Resistance to at least one of the following antibiotics was found in eight wild-type strains of Aerococcus viridans: erythromycin (six strains), tetracycline and minocycline (five strains), chloramphenicol (one strain), and high levels of streptomycin (one strain). None of the strains transferred any of their antibiotic resistance markers into streptococcal, enterococcal, or A. viridans recipients by conjugation. By DNA-DNA hybridization experiments, the ermB gene of transposon Tn917, of Enterococcus faecalis origin, was detected in five of the six strains resistant to erythromycin and was localized for one strain on the chromosome and for four strains on nonconjugative small (4.7- to 4.9-kilobase) plasmids. The tetM gene of the conjugative transposon Tn916, of E. faecalis origin, was localized on the chromosome of four of the five strains resistant to tetracycline and minocycline; in three of these strains a structure similar to that of Tn916 was found. Homology to the tetO gene of pUA466, of Campylobacter jejuni origin, was detected on the chromosome of the fifth strain. No sequence homology was detected in any strain with probes corresponding to the tetL gene of group B Streptococcus origin, to the ermA gene of the transposon Tn554 of Staphylococcus aureus origin, or to the cat genes of either pC194 or pC221 of S. aureus origin.
Influence of protein binding on therapeutic efficacy of cefoperazone
Authors: Peterson L R , Moody J A , Fasching C E , Gerding D N
Published: June 2012

The effect of protein binding of cefoperazone (89.3% bound to rabbit serum) on antibacterial activity in serum was tested in a model that simulated a closed-space infection in a neutropenic host. Four gram-negative bacilli were tested in the model with cefoperazone doses of 20 and 200 mg/kg administered intramuscularly every 6 h for 16 doses. Cefoperazone efficacy was measured at 92 h by determining the log10 decrease in bacterial count from that of the control for five paired studies with three isolates. A significantly better response was demonstrated when the free (non-protein-bound) drug concentration exceeded the MICs and MBCs for the infecting microorganisms at the infection site at all times (P less than 0.005). This supports the concept that free (unbound) drug is the active component in treating bacterial infections.
Antibacterial activity of trospectomycin (U-63366F) and initial evaluations of disk diffusion susceptibility tests
Authors: Barry A L , Jones R N , Thornsberry C
Published: June 2012

The in vitro activities of trospectomycin sulfate were compared with those spectinomycin against 632 aerobic microorganisms, including 66 Neisseria gonorrhoeae isolates. Against species other than gram-negative bacilli, trospectomycin was about 4- to 16-fold more active than spectinomycin. For disk diffusion tests, a 30-micrograms disk is recommended, with tentative zone size breakpoints of less than or equal to 13 mm for resistance (MIC, greater than or equal to 64 micrograms/ml) and greater than or equal to 17 mm for susceptibility (MIC, less than or equal to 16 micrograms/ml).
Inhibition of enoxacin absorption by antacids or ranitidine
Authors: Grasela T H , Schentag J J , Sedman A J , Wilton J H , Thomas D J , Schultz R W , Lebsack M E , Kinkel A W
Published: June 2012

Ten normal volunteers participated in a randomized, five-way crossover study to determine the effect of concurrent enoxacin and antacid or ranitidine administration on enoxacin absorption. The bioavailability of a single oral 400-mg enoxacin dose was significantly decreased, by 73 and 49%, when Maalox TC was administered 0.5 and 2 h before enoxacin, respectively. Enoxacin bioavailability was not significantly altered when the antacid was given 8 h before or 2 h after enoxacin administration. Ranitidine, administered intravenously 2 h before enoxacin, also significantly decreased enoxacin bioavailability, by 40%. The correlation between the proximity of antacid administration and the magnitude of the decrease in enoxacin bioavailability supports complexation as the mechanism of the antacid-enoxacin interaction. However, reduction of enoxacin bioavailability by ranitidine suggests that elevated gastric pH may also play a role in the antacid-enoxacin drug-drug interaction.
Susceptibility of Coxiella burnetii to pefloxacin and ofloxacin in ovo and in persistently infected L929 cells
Authors: Raoult D , Yeaman M R , Baca O G
Published: June 2012

The relative lack of efficacy of the antibiotic treatment of chronic Q fever endocarditis justifies the further evaluation of the susceptibility of Coxiella burnetii to the modern quinolone antibiotics. We evaluated the efficacies of pefloxacin and ofloxacin in controlling the Nine Mile isolate of C. burnetii by using an embryonated egg assay and persistently infected L929 cells in culture. Pefloxacin was effective in controlling the intracellular parasite at a concentration of 50 micrograms per egg and 1 microgram/ml in cultures of infected cells. Ofloxacin was effective at a concentration of 25 micrograms per egg and 0.5 microgram/ml in infected-cell cultures. In light of the fact that the concentrations of antibiotics used fall within physiological ranges used in humans, ofloxacin and pefloxacin may be useful in the clinical management of chronic Q fever, for which, to date, results have been poor.
Effect of peptide AS-48 on Enterococcus faecalis subsp. liquefaciens S-47
Authors: Galvez A , Valdivia E , Martinez M , Maqueda M
Published: June 2012

The enterococcal peptide AS-48 exerts a concentration-dependent bactericidal effect on Enterococcus faecalis subsp. liquefaciens S-47; cell rescue by cardiolipin and trypsin can be effected only in the first few minutes after antibiotic addition. Gramicidin-exposed cells are protected from killing by AS-48. Long-term and pulse incorporation of radiolabeled substrates into trichloroacetic acid-precipitable material, O2 consumption, and the ability to maintain intracellular potassium levels are impaired shortly after addition of AS-48.
In vitro effects of antimicrobial agents on Mycobacterium leprae in mouse peritoneal macrophages
Authors: Ramasesh N , Krahenbuhl J L , Hastings R C
Published: June 2012

Mycobacterium leprae synthesizes large quantities of a specific phthiocerol-containing phenolic glycolipid in vivo. We have shown earlier that viable M. leprae readily incorporates radiolabeled palmitic acid into phenolic glycolipid I when residing in cultured macrophages in vitro and that this process is inhibited by the antileprosy drug rifampin. In the present paper we report that application of this observation to the rapid evaluation of over 25 antimicrobial agents for potential antileprosy activity in vitro. All the known antileprosy drugs rifampin, dapsone, clofazimine, and ethionamide inhibited phenolic glycolipid I synthesis. Rifabutin, a spiropiperidyl derivative of rifamycin, also reported to be active in the mouse model, was very effective. Interestingly, the macrolides erythromycin, clarithromycin, and roxithromycin were also found to be active in this system, while D-cycloserine and other cell wall synthesis inhibitors showed no effect. Many of the compounds found to be active in this system have been reported to be effective in vivo in mice. This correlation lends support to the feasibility of using phenolic glycolipid I synthesis for the rapid evaluation of new drugs against leprosy.
Chemical characterization of an antimicrobial substance produced by Lactobacillus reuteri
Authors: Talarico T L , Dobrogosz W J
Published: June 2012

Lactobacillus reuteri converts glycerol into a potent cell growth inhibitor. This substance, termed reuterin, inhibits the growth of gram-positive and gram-negative bacteria as well as yeasts, fungi, and protozoa. Semipreparative chromatography was used to purify reuterin, and Fourier transform infrared spectroscopy and liquid chromatography-mass spectrometry were used to establish the molecular weight as well as the molecular functionality of the reuterin molecule. Nuclear magnetic resonance studies of purified reuterin carried out with deuterium oxide confirmed the presence of two three-carbon compounds, beta-hydroxypropionaldehyde and the corresponding hydrated acetal, and a six-carbon cyclic dimer of the aldehyde. Further nuclear magnetic resonance studies with deuterated methanol revealed that in this solvent the compound existed as a three-carbon compound in a methoxy form. Trimethylsilyl derivatives of reuterin were analyzed by gas chromatography-mass spectrometry, and a molecule was identified which had a molecular weight corresponding to a disilylated dimeric structure. On the basis of the above information, reuterin was determined to be an equilibrium mixture of monomeric, hydrated monomeric, and cyclic dimeric forms of beta-hydroxypropionaldehyde. This was subsequently confirmed by chemical synthesis.
Influence of fluoroquinolones on expression and function of P fimbriae in uropathogenic Escherichia coli
Authors: Kovarik J M , Hoepelman I M , Verhoef J
Published: June 2012

P fimbriae are the major adhesins mediating attachment of pyelonephritogenic Escherichia coli to urinary tract tissues, and they therefore constitute a recognized virulence factor. In this work, the effect of fluoroquinolones on P fimbria expression and function in E. coli SS142 and C1212 was assessed. Ciprofloxacin, fleroxacin, and norfloxacin were compared with their precursor nalidixic acid and with trimethoprim in sublethal concentrations ranging from 1/32 to 1/4 of the MIC. Fimbria function was assessed in a standard hemagglutination assay and in a parallel hemagglutination inhibition assay in which the tier of antifimbrial antiserum necessary to inhibit hemagglutination by SS142 was determined. Adhesion of antibiotic-exposed bacteria to human uroma T24 cells in suspension was also measured. Fimbria production was quantitated in an inhibition enzyme-linked immunosorbent assay. Trimethoprim produced a dose-dependent decrease of three to four hemagglutination titers for both strains and a decline in the antiserum titer from 1:16 (control) to 1:128 (1/4 MIC) for E. coli SS142. Adherence exhibited similar decrements from 130 +/- 28 (control) to 16 +/- 3 (1/4 MIC) and from 83 +/- 19 (control) to 30 +/- 11 (1/4 MIC) E. coli cells per uroepithelial cell (mean +/- standard error) for SS142 and C1212, respectively (P less than 0.015). By enzyme-linked immunosorbent assay, the inhibition following exposure decreased in a dose-dependent manner from 31% (control) to 8% (1/4 MIC). By contrast, none of the quinolones produced significant changes in the parameters assessed above. At sublethal concentrations, trimethoprim decreased fimbria production. Following exposure to fluoroquinolones, however, E. coli expressed morphologically and functionally intact P fimbriae.
Multifactorial analysis of effects of interactions among antifungal and antineoplastic drugs on inhibition of Candida albicans growth
Authors: Ghannoum M A , Motawy M S , Abu Hatab M A , Ibrahim A S , Criddle R S
Published: June 2012

Interactions among antineoplastic and antifungal drugs affecting the inhibition of Candida albicans growth are complex functions of the nature of the drugs used in combination, their absolute concentrations, and also their relative concentrations. Studies of drug interactions involving the use of test drugs in fixed concentration ratios can lead to inaccurate conclusions about synergism or antagonism among the drugs. A multifactorial experimental design procedure in which the concentrations of all drugs in test combinations were simultaneously varied has been used to identify and quantify drug interactions. The methods have been applied to combinations of two, three, and four drugs, including antineoplastic drugs, antifungal drugs, and combinations of antineoplastic and antifungal drugs. Results were obtained which allow predictions of effects of combinations and provide maximum effectiveness in growth inhibition with minimum levels of the test drugs.
Organization of complex transposon Tn2610 carrying two copies of tnpA and tnpR
Authors: Yamamoto T
Published: June 2012

Transposon Tn2610 has two elements of 3.5 kilobase pairs as inverted repeats, one set at each end. This unique terminal element contained the transposition genes tnpA and tnpR. Only the tnpA gene in the left element was functional for transposition, whereas both tnpR genes were active. Possible evolutionary relationships among class II transposable elements are proposed on the basis of the genetic and structural organization of Tn2610.
In vitro activities of amifloxacin and two of its metabolites
Authors: Venezia R A , Prymas L A , Shayegani A , Yocum D M
Published: June 2012

Amifloxacin and two of its metabolites, N-desmethyl amifloxacin and amifloxacin N-oxide, were evaluated by a microdilution MIC susceptibility test against 500 clinical isolates and compared with ciprofloxacin, lomefloxacin, norfloxacin, aztreonam, and imipenem. Of the Staphylococcus species isolates, 208 were methicillin resistant; the MICs for 78 of the isolates of the family Enterobacteriaceae were greater than or equal to 64 micrograms of cefazolin, ampicillin, piperacillin, and mezlocillin per ml. Based on our results, amifloxacin had activity equivalent to those of norfloxacin and lomefloxacin but was less active than ciprofloxacin. The N-oxide metabolite was the least active; however, for the majority of gram-negative bacteria, N-desmethyl amifloxacin was as active as amifloxacin.
Ceftriaxone-netilmicin combination in single-daily-dose treatment of experimental Escherichia coli endocarditis
Authors: Fantin B , Pangon B , Potel G , Vallois J M , Caron F , Bure A , Carbon C
Published: June 2012

We evaluated the activities of ceftriaxone (15 mg/kg), netilmicin (6 mg/kg), and their combination given intramuscularly once daily for 4 days for the treatment of experimental Escherichia coli endocarditis in rabbits. In vitro, a greater rate of killing and an increased trough serum bactericidal titer (P less than 0.01) were achieved with the combination. In vivo, the combination had a greater bactericidal effect (P less than 0.01) and resulted in a greater number of sterile vegetations (P less than 0.05) than single-drug therapy. Thus, in vivo, an increased effect can be obtained despite a single daily dose of a long-acting cephalosporin and an aminoglycoside.
Inhibition of human immunodeficiency virus in vitro by combinations of 3'-azido-3'-deoxythymidine and foscarnet
Authors: Koshida R , Vrang L , Gilljam G , Harmenberg J , Oberg B , Wahren B
Published: June 2012

We describe a synergistic effect of combinations of foscarnet and 3'-azido-3'-deoxythymidine against human immunodeficiency virus type 1 multiplication in cell culture, an additive effect of foscarnet and 3'-azido-3'-deoxythymidine triphosphate against human immunodeficiency virus type 1 reverse transcriptase, and a low toxicity in cell culture of combinations of the two drugs.
Pharmacokinetics of subcutaneous azidothymidine in rhesus monkeys
Authors: Balis F M , McCully C , Gough L , Pizzo P A , Poplack D G
Published: June 2012

The pharmacokinetics of subcutaneous bolus and continuous infusion azidothymidine (AZT) was studied in rhesus monkeys. Three animals received 100 mg/m2 as a bolus injection both intravenously and subcutaneously, with the order of administration randomly determined. Two animals received a continuous subcutaneous infusion of 25 mg/m2 per h for 12 or 24 h. AZT was measured in plasma by a reverse-phase high-pressure liquid chromatographic assay. Following intravenous bolus administration, AZT elimination was rapid, with a mean half-life of 1.2 h and a mean clearance of 318 ml/min per m2 (range, 200 to 441 ml/min per m2). The bolus subcutaneous dose was rapidly (time to peak concentration, 15 to 30 min) and nearly completely (fraction absorbed, 92%) absorbed without evidence of local tissue toxicity. With continuous subcutaneous infusion of AZT, the steady state was attained within 4 h and steady-state concentrations in plasma in the two animals exceeded 3.0 mumol/liter. No local tissue toxicity was observed at the infusion site. The subcutaneous route may be a practical alternative to intravenous administration of AZT and deserves further clinical study.
Comparison of N-methylthiotetrazole dispositions in healthy volunteers following single intravenous doses of moxalactam, cefoperazone, and cefotetan
Authors: Welage L S , Hejmanowski L G , Wilton J H , Walawander C , Rigan D , Williams J S , Schentag J J
Published: June 2012

The N-methylthiotetrazole side chain (NMTT) that is present on several cephalosporins has been implicated in the development of antibiotic-associated hypoprothrombinemia. A randomized three-way crossover trial was conducted to compare the release of the NMTT side chain from three NMTT-containing antibiotics. Single 2-g doses of moxalactam, cefoperazone, and cefotetan were given, followed by serial blood and urine sampling. The concentrations of the parent compound and the NMTT side chain in plasma, urine, and the reconstituted antibiotic solution were determined by high-pressure liquid chromatography. Peak NMTT concentrations ranged from 0.42 to 16.50 micrograms/ml and were significantly higher after moxalactam administration than after cefoperazone or cefotetan administration (P less than 0.01). The NMTT trough concentrations (12.5 h) ranged from nondetectable to 2.47 micrograms/ml and tended to be greater following cefoperazone administration. The amounts of NMTT administered (e.g., the amount in the reconstituted antibiotic solution) were 25.8 +/- 1.4, 15.2 +/- 0.9, and 22.1 +/- 3.0 mg following moxalactam, cefoperazone, and cefotetan administration, respectively (P less than 0.01). In contrast, urinary recoveries of NMTT were 57.4 +/- 26.2, 73.6 +/- 44.3, and 29.7 +/- 22.9 mg following moxalactam, cefoperazone, and cefotetan, respectively. The amount of NMTT formed in vivo and excreted unchanged, as assessed by subtracting in vitro NMTT formation from NMTT urinary recovery, was significantly higher after cefoperazone than after moxalactam or cefotetan administration (P less than 0.05). The discrepancy between in vitro NMTT production (moxalactam > cefotetan > cefoperazone) and the amount of NMTT formed in vivo and excreted unchanged (cefoperazone > moxalactam > cefotetan) demonstrated that the in vivo production of NMTT is dependent on the disposition of the parent cephalosporin.
Effect of acyclovir on radiation- and chemotherapy-induced mouth lesions
Authors: Bubley G J , Chapman B , Chapman S K , Crumpacker C S , Schnipper L E
Published: June 2012

Several chemotherapeutic regimens and radiation therapy, if delivered to the oral mucosa, are associated with a high frequency of mouth lesions. The cause of this side effect is not known for certain, but in past studies it has sometimes been associated with the ability to culture herpes simplex virus type 1 from the mouth. In a double-blind prospective trial, patients with head and neck tumors treated with chemotherapy or radiation therapy were treated with either acyclovir or placebo. Although the frequency of culture-positive herpes simplex virus was low in the untreated group, it was significantly lower, zero, in the acyclovir-treated group. However, there were no differences in the frequency or type of mouth lesions experienced by patients receiving either radiation or chemotherapy who were taking acyclovir or placebo. These results suggest that herpes simplex virus is not a frequent cause or complication of oral lesions afflicting this patient population.
Evaluation of teicoplanin for treatment of endocarditis caused by gram-positive cocci in 20 patients
Authors: Leport C , Perronne C , Massip P , Canton P , Leclercq P , Bernard E , Lutun P , Garaud J J , Vilde J L
Published: June 2012

Teicoplanin, a new glycopeptide antibiotic similar to vancomycin, was evaluated for the treatment of bacterial endocarditis in an open multicenter study from May 1985 to August 1987. A total of 20 patients with positive blood culture endocarditis received teicoplanin once daily as a mean intravenous injection of 7.3 mg/kg of body weight (range, 4.8 to 10.6 mg/kg); in 17 patients, teicoplanin was combined with another antibiotic, usually an aminoglycoside. The mean duration of therapy was 28 days (range, 7 to 66 days). The diagnosis of endocarditis was confirmed by echocardiography or anatomical findings in 15 patients and established on the basis of clinical manifestations plus positive blood cultures in 5 patients. The tricuspid valve was involved in 11 of the 20 patients. Isolates from blood were 12 Staphylococcus aureus, 1 Staphylococcus hominis, 1 Micrococcus sedentarius, 1 Enterococcus faecalis, 3 Streptococcus bovis, and 2 nongroupable Streptococcus sp. At the end of therapy, bacterial eradication was achieved in 17 of 20 patients (85%), and a favorable clinical outcome had occurred in 14 of 17 evaluable patients (82%). Of these 14 patients, one relapsed 4 months after the end of treatment. Thus, teicoplanin was effective in 13 of 17 patients (76%). Mean peak levels of teicoplanin in serum were lower, 23.1 +/- 2.9 micrograms/ml, in patients who failed than in those who were cured (45.8 +/- 8.4 micrograms/ml). Side effects occurred in 7 of 20 patients (35%), and required premature discontinuation of teicoplanin in 3 patients. These side effects were fever in three patients, rash in three patients, hearing loss in two patients, and increased serum transaminase levels in two patients. This study demonstrates the efficacy of teicoplanin in the treatment of endocarditis and the need for achieving peak levels in serum close to 40 micrograms/ml. Teicoplanin should now be further evaluated in endocarditis caused by gram-positive cocci means of controlled comparative study with standard therapy.
Single-dose enoxacin compared with 3-day treatment for urinary tract infection
Authors: Backhouse C I , Matthews J A
Published: June 2012

Oral treatment of simple urinary tract infections generally involves 5 to 7 days of antibiotic therapy. This study with enoxacin, a new antibacterial agent of the quinolone-azaquinolone class, investigated the efficacy of a single dose compared with 3 days of treatment. A total of 154 outpatients with symptoms of simple cystitis were treated in an open randomized study with enoxacin, either one 600-mg dose or 200 mg twice a day for 3 days. A urine sample was collected for culture before treatment, 7 to 10 days after treatment, and 4 to 6 weeks after treatment. Seventy-three patients had positive bacterial cultures from the pretreatment urine sample; the predominant pathogen was Escherichia coli, along with a number of other gram-negative organisms and Staphylococcus spp. Of these patients, 33 received a single dose of enoxacin and 40 were treated for 3 days. Follow-up examination at 7 to 10 days showed negative urine cultures in 76% of patients from the single-dose group and 89% from the multiple-dose group, a difference that was not statistically significant (P = 0.665, Fisher's exact test). A number of patients were lost to follow-up at 4 to 6 weeks. However, of those who did attend, only three patients were shown to have relapsed or become reinfected (two in the multiple-dose group and one in the single-dose group). Enoxacin was well tolerated in both groups of patients; the few adverse events were mostly mild.
In vitro susceptibility of Bordetella parapertussis to various antimicrobial agents
Authors: Watanabe M , Haraguchi Y
Published: June 2012

The in vitro activity of 18 antimicrobial agents against 32 strains of Bordetella parapertussis isolated from whooping cough patients was studied. The most active antimicrobial agents were piperacillin and minocycline, followed (in descending order of activity) by moxalactam, erythromycin, cefoperazone, tetracycline, ampicillin, cefotaxime, chloramphenicol, josamycin, sulfamethoxazole, and nalidixic acid. Isolates were resistant to benzylpenicillin, cephalothin, cefatrizine, cefaclor, streptomycin, and cephalexin.
Biliary and pancreatic excretion of cefamandole
Authors: Burns G P , Stein T A , Cohen M
Published: June 2012

After intravenous infusion of secretin and cholecystokinin in six dogs, cefamandole (50 mg/kg of body weight) was given intravenously for 10 min. Samples of serum, bile, pancreatic juice, liver, pancreas, fat, and muscle were collected over a 2-h period. Cefamandole levels were measured by a microbiological assay. The highest levels were as follows: serum, 160 micrograms/ml; bile, 3,071 micrograms/ml; pancreatic juice, 7 micrograms/ml; liver, 101 micrograms/g; pancreas, 44 micrograms/g; muscle, 20 micrograms/g; and fat, 14 micrograms/g. Levels in pancreatic juice were extremely low compared with levels in pancreatic tissue, suggesting the existence of a barrier to excretion at the ductal membrane.
Penicillin-binding proteins of Haemophilus ducreyi
Authors: Lee B C , Bryan L E
Published: June 2012

The penicillin-binding protein (PBP) profile of Haemophilus ducreyi was determined by a whole-cell-labeling assay. Only two major PBPs, of molecular weights 90,000 (PBP 1) and 38,500 (PBP 2), were detected in six of eight strains studied. Competition binding experiments and the attendant morphological effects suggested that PBP 1 was either a functional amalgamation or a lack of resolution of two proteins equivalent to PBPs 1 and 3 of Escherichia coli.
Prospective, randomized, placebo-controlled trial of norfloxacin for the prophylaxis of recurrent urinary tract infection in women
Authors: Nicolle L E , Harding G K , Thompson M , Kennedy J , Urias B , Ronald A R
Published: June 2012

Thirty women were randomized in a double-blind, placebo-controlled study to receive either norfloxacin, 200 mg orally daily at bedtime, or placebo for the prevention of recurrent bladder infection. Subjects were followed monthly to monitor compliance and symptoms, for urine culture and periurethral and anal canal swabs to monitor colonization, and for blood specimens for hematologic and biochemical studies to monitor safety. During 1 year of follow-up, 10 of 15 placebo subjects and none of 15 norfloxacin subjects developed infection (P less than 0.001). Adverse effects occurred with equal frequencies in the two groups. For norfloxacin subjects, only 2 (1.6%) of 129 periurethral and 4 (3.1%) of 129 anal canal swabs showed colonization with aerobic gram-negative organisms, while 16 (22%) of 73 periurethral and 47 (64%) of 73 anal canal swabs from placebo subjects showed colonization. Daily therapy with norfloxacin at bedtime is effective in preventing recurrent cystitis. During 1 year of norfloxacin therapy, colonization was infrequent and superinfection with norfloxacin-resistant organisms did not occur.