Floxacin was shown to have significant antimicrobial activity in numerous experimental infection models 1, 18, 19, ; . Early clinical studies have demonstrated its effectiveness in a variety of infections, including uncomplicated gonorrhea, at single oral doses as low as 50 mg 22 ; . Single- and multiple-dose safety and pharmacokinetic studies with healthy humans have demonstrated that the drug is well tolerated and that a dosage of 200 mg once or twice daily should be adequate for the treatment of systemic infections caused by most common bacterial pathogens 38, 39, 45 ; . Studies of the tissue distribution of trovafloxacin in laboratory animals have demonstrated rapid absorption from the gastrointestinal tract unpublished results ; and high concentrations in virtually all tissues 12 ; . For humans, concentrations of trovafloxacin have been measured in bodily fluids and a small number of tissues 29, 40 ; . However, detailed studies of tissue distribution have not been reported. To optimize the clinical use of trovafloxacin, detailed pharmacokinetic data on the distribution of drug to different tissues would be of considerable value in designing dosing schedules that maximize therapeutic efficacy for different types of infection. Positron emission tomography PET ; is an extremely powerful in vivo technique for making detailed pharmacokinetic measurements in both animal models of infection and humans 10, 11, 1315, ; . Since trovafloxacin contains three.
Time to peak concentration: alatrofloxacin injection measured as trovafloxacin ; : following a single 1-hour infusion of 200 mg: 1 hour.
Nagai, K., T.A. Davies, G.A. Pankuch, B.E. DeWasse, M.R. Jacobs, and P.C. Appelbaum. 2000. In vitro selection pf resistance to clinafloxacin, ciprofloxacin, and trovafloxacin in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 44.
MATERIALS AND METHODS Bacterial strains. Two clinical isolates of penicillin-resistant MIC, 2 g ml ; and macrolide-resistant MIC, 6 g ml ; S. pneumoniae isolates 68 and 79 ; were obtained from two patients treated at Detroit Receiving Hospital. Antibiotics. Trovafloxacin lot no. 25381-086-02 ; was supplied by Pfizer Inc, Groton, Conn. Gatifloxacin lot no. 331 ; was supplied by Bristol-Myer Squibb Pharmaceutical, New Brunswick, N.J. Clinafloxacin lot no. PD127391-0002 Lot J ; was supplied by Parke-Davis Pharmaceutical Research, Ann Arbor, Mich. Sparfloxacin lot no. 721A ; was supplied by Rhone-Poulenc Rorer, Collegeville, Pa. Levofloxacin lot no. N-8018 ; was supplied by Ortho-McNeil Pharmaceutical, Raritan, N.J. Ciprofloxacin for injection lot no. 851640 ; was supplied by Bayer Corporation, West Haven, Conn. E-strips. Trovafloxacin lot no. B62424 ; , gatifloxacin lot no. B72030 ; , clinafloxacin lot no. B72330 ; , sparfloxacin lot no. B52046 ; , levofloxacin lot no. B71753 ; , and ciprofloxacin lot no. B52049 ; E-strips were supplied by AB Biodisk North America Inc., Piscataway, N.J. Media. Mueller-Hinton broth Difco Laboratories, Detroit, Mich. ; supplemented with calcium 25 mg liter ; and magnesium 12.5 mg liter ; SMHB ; plus 5% lysed horse blood LHB ; Rockland, Inc., Gilbertsville, Pa. ; was used for all susceptibility testing. Todd-Hewitt broth THB ; Difco Laboratories ; supplemented with calcium 6 mg liter ; and 0.5% yeast extract Difco Laboratories ; was used for susceptibility testing and in the in vitro infection models. Susceptibility testing. MICs and minimal bactericidal concentrations MBCs ; of all of the antibiotics were determined in quadruplicate by broth microdilution in SMHB plus 5% LHB according to National Committee for Clinical Laboratory Standards guidelines 16 ; . MICs and MBCs were also determined in THB supplemented with yeast. The trovafloxacin MIC and MBC were determined in presence of albumin 4 g dl ; account for protein binding of the drug. Samples 5 l ; from clear wells were plated onto tryptic soy agar TSA ; plates with 5.
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And the pilot likewise, in the strict sense of the term, is a ruler of sailors and not a mere sailor? That has been admitted. And such a pilot and ruler will provide and prescribe for the interest of the sailor who is under him, and not for his own or the ruler's interest? He gave a reluctant 'Yes.' Then, I said, Thrasymachus, there is no one in any rule who, in so far as he is ruler, considers or enjoins what is for his own interest, but always what is for the interest of his subject or suitable to his art; to that he looks, and that alone he considers in everything which he says and does. When we had got to this point in the argument, and every one saw that the definition of justice had been completely upset, Thrasymachus, instead of replying to me, said: Tell me, Socrates, have you got a nurse? Why do you ask such a question, I said, when you ought rather to be answering? Because she leaves you to snivel, and never wipes your nose: she has not even taught you to know the shepherd from the sheep. What makes you say that? I replied. Because you fancy that the shepherd or neatherd fattens or tends the sheep or oxen with a view to their own good and not to the good of himself or his master; and you further imagine that the rulers of states, if they are true rulers, never think of their subjects as sheep, and that they are not studying their own advantage day and night. Oh, no; and so entirely astray are you in your ideas about the just and unjust as not even to know that justice and the just are in reality another's good; that is to say, the interest of the ruler and stronger, and the loss of the subject and servant; and injustice the opposite; for the unjust is lord over the truly simple and just: he is the stronger, and his subjects do what is for his interest, and minister to his happiness, which is very far from being their own. Consider further, most foolish Socrates, that the just is always a loser in comparison with the unjust. First of all, in private contracts: wherever the unjust is the partner of the just you will find that, when the partnership is dissolved, the unjust man has always more and the just less. Secondly, in their dealings with the State: when there is an income-tax, the just man will pay more and the unjust less on the same amount of income; and when there is anything to be received the one gains nothing and the other much. Observe.
REFERENCES 1. Appelbaum, P. C. 1992. Antimicrobial resistance in Streptococcus pneumoniae: an overview. Clin. Infect. Dis. 15: 7783. 2. Appelbaum, P. C. 1996. Emergence of resistance to antimicrobial agents in gram-positive bacteria--pneumococci. Drugs 51 Suppl. 1 ; : 15. 3. Azoulay-Dupuis, E., E. Vallee, B. Veber, J. P. Bedos, J. Bauchet, and J. J. Pocidalo. 1992. In vivo efficacy of a new fluoroquinolone, sparfloxacin, against penicillin-susceptible and -resistant and multiresistant strains of Streptococcus pneumoniae in a mouse model of pneumonia. Antimicrob. Agents Chemother. 36: 26982703. 4. Bedos, J. P., V. Rieux, J. Bauchet, M. Muffat-Joly, C. Carbon, and E. Azoulay-Dupuis. 1998. Efficacy of trovafloxacin against penicillin-susceptible and multiresistant strains of Streptococcus pneumoniae in a mouse pneumonia model. Antimicrob. Agents Chemother. 42: 862867. 5. Boswell, F. J., J. M. Andrews, and R. Wise. 2001. Comparison of the in vitro activities of BMS-284756 and four fluoroquinolones against Streptococcus pneumoniae. J. Antimicrob. Chemother. 48: 446447. 6. Brenwald, N. P., M. J. Gill, and R. Wise. 1998. Prevalence of a putative efflux mechanism among fluoroquinolone-resistant clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 42: 20322035. 7. Clark, C. L., K. Nagai, T. A. Davies, B. Bozdogan, B. Dewasse, M. R. Jacobs, and P. C. Appelbaum. 2002. Single- and multistep selection study of the antipneumococcal activity of BMS-284756 compared to ciprofloxacin, levofloxacin, trovafloxacin and moxifloxacin. Clin. Microbiol. Infect. 8: 373380. 8. Forrest, A., D. E. Nix, C. H. Ballow, T. F. Goss, M. C. Birmingham, and J. J. Schentag. 1993. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob. Agents Chemother. 37: 10731081. 9. Gales, A., H. Sader, R. N. Jones, and SENTRY Participants Group Latin America ; . 2001. Activities of BMS 284756 T-3811 ; against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae isolates from SENTRY Antimicrobial Surveillance Program medical centers in Latin America 1999 ; . Antimicrob. Agents Chemother. 45: 14631466 and truvada.
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Rofloxacin, and norfloxacin. This type of mutant possessed single-point mutations in the QRDR of the parC gene and was cross-resistant to the selecting agents but was not resistant to gatifloxacin and sparfloxacin. The decreases in the activities of trovafloxacin, norfloxacin, ciprofloxacin, and levofloxacin against these parC mutants were four-, four-, four-, and twofold, respectively. The second type of mutant type II ; comprised strains selected by gatifloxacin or sparfloxacin. These mutants possessed single-point mutations in the QRDR of the gyrA gene and were cross-resistant to the selecting agents but were not resistant to the other fluoroquinolones tested. The decreases in the activities of gatifloxacin and sparfloxacin against the gyrA mutants were two- and eightfold, respectively. This decrease in the activity of sparfloxacin against the gyrA mutants corresponds with those reported by Pan and Fisher 14 ; . The third type of mutant type III ; comprised those mutants selected with trovafloxacin. The mutants possessed no mutation in the QRDR of the target genes gyrA, gyrB, parC, and parE ; . These mutants were resistant to trovafloxacin and sparfloxacin and formed colonies that were smaller than those of the parent and the other mutant strains. Some investigators have reported on quinolone-resistant mutant strains of S. pneumoniae that possess no mutation in the QRDRs of the gyrA, gyrB, parC, and or parE genes, which suggests that these particular strains are permeability efflux ; mutants 2, 12, 13 and tums.
Concomitant sucralfate administration 1g ; with trovafloxacin 200 mg p.o. resulted in a 70% decrease in trovafloxacin systemic exposure AUC ; and a 77% reduction in peak serum concentration Cmax ; . See PRECAUTIONS: Drug Interactions, DOSAGE AND ADMINISTRATION. ; Concomitant administration of ferrous sulfate 120 mg elemental iron ; with trovafloxacin 200 mg p.o. resulted in a 40% reduction in trovafloxacin systemic exposure AUC ; and a 48% decrease in trovafloxacin Cmax. See PRECAUTIONS: Drug Interactions, DOSAGE AND ADMINISTRATION. ; Concomitant administration of intravenous morphine 0.15 mg kg ; with oral trovafloxacin 200 mg ; resulted in a 36% reduction in trovafloxacin AUC and a 46% decrease in trovafloxacin Cmax. Trovafloxacin administration had no effect on the pharmacokinetics of morphine or its pharmacologically active metabolite, morphine6--glucuronide. See PRECAUTIONS: Drug Interactions, DOSAGE AND ADMINISTRATION. ; Minor pharmacokinetic interactions that are most likely without clinical significance include calcium carbonate, omeprazole, and caffeine. Concomitant administration of calcium carbonate 1000 mg ; with trovafloxacin 200 mg p.o. resulted in a 20% reduction in trovafloxacin AUC and a 17% reduction in peak serum trovafloxacin concentration Cmax ; . A 40-mg dose of omeprazole given 2 hours prior to trovafloxacin 300 mg p.o. ; resulted in a 17% reduction in trovafloxacin AUC and a 17% reduction in trovafloxacin peak serum concentration Cmax ; . Administration of trovafloxacin 200 mg ; concomitantly with caffeine 200 mg ; resulted in a 17% increase in caffeine AUC and a 15% increase in caffeine Cmax. These changes in caffeine exposure are not considered clinically significant. No significant pharmacokinetic interactions include cimetidine, theophylline, digoxin, warfarin, and cyclosporine. Cimetidine co-administration 400 mg twice daily for 5 days ; with trovafloxacin 200 mg p.o. daily for 3 days ; resulted in changes in trovafloxacin AUC and Cmax of less than 5%. Trovafloxacin 200 mg p.o. daily for 7 days ; co-administration with theophylline 300 mg twice daily for 14 days ; resulted in no change in theophylline AUC and Cmax. Trovafloxacin 200 mg p.o. daily for 10 days ; co-administration with digoxin 0.25 mg daily for 20 days ; did not significantly alter systemic exposure AUC ; to digoxin or the renal clearance of digoxin.
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REFERENCES 1. Buggy, B. P., D. R. Schaberg, and R. D. Swartz. 1984. Intraleukocytic sequestration as a cause of persistent Staphylococcus aureus peritonitis in continuous ambulatory peritoneal dialysis. Am. J. Med. 76: 10351040. 2. Child, J., J. Andres, F. Boswell, N. Brenwald, and R. Wise. 1995. The in vitro activity of CP 99, 219, a new naphthyridone antimicrobial agent: a comparison with fluoroquinolone agents. J. Antimicrob. Chemother. 35: 869876. 3. Edelstein, P. H., M. A. Edelstein, J. Ren, R. Polzer, and R. P. Gladue. 1996. Activity of trovafloxacin CP-99, 219 ; against Legionella isolates; in vitro activity, intracellular accumulation and killing in macrophages, and pharmacokinetics and treatment of guinea pigs with L. pneumophila pneumoniae. Antimicrob. Agents Chemother. 40: 314319. 4. Garci I., A. Pascual, M. C. Guzman, and E. J. Perea. 1992. Uptake and a, intracellular activity of sparfloxacin in human polymorphonuclear leukocytes and tissue culture cells. Antimicrob. Agents Chemother. 36: 10531056. 5. Garci I., A. Pascual, and E. J. Perea. 1994. Intracellular penetration and a, activity of BAY Y 3118 in human polymorphonuclear leukocytes. Antimi and tysabri.
Though delicate in color, these gardener favorites are hearty and easy to maintain. lJune Grass koeleria cristata ; lLittle Bluestem andropogon scoparius ; lPale Coneflower echinicea pallida ; lPrairie Smoke geum triflorum ; lGrand Penstemon penstemon grandiflora
Only palladium compoundsform melts; other products do not melt in vacuum over the hottest gas flame available-in contrast to published accounts-indeed, they tend to dissociateat very high temperatures. The platinum metal tellurides RuTe2, OsTe2, RhTe21o, and IrTe21, all belong structurally to the pyrite group. Their interplanar spacings as well as the densities of their lines on tr-ray powder photographs are consequent ly very similar; the unit cell edgesare within the range 6.377 a036.428 A. The ditelluridesof platinum and palladium are both hexagonal and belong to the cadmium iodide type which is characterized by a parallel 0001 ; .IrTe and PdTe have niccolite structures. strong cleavage Properties determined on all products are shown in Table 7. RnlBnBNcns and ubiquinone.
Boilersuit impermanence was 24% in the trovafloxacin chemical group and 25% in the comparator unit.
With his or her arms extended out of the field of view. For imaging of the extracranial organs, the subject was positioned on the basis of reconstructed transmission data so that the organs of interest were included in the field of view. For later imaging, positioning marks were drawn on the subject's thorax, abdomen, and pelvis. During the first 2 h, serial 2-min images of both organ groups were acquired. The bed positions corresponding to the two body regions ; were switched under computer control. After the last image was acquired the subject was allowed to resume usual activity. At 4 and 6 to 8 after the start of the infusion, the subject was repositioned in the PET camera, and 10- to 15-min images were acquired in each position. A transmission scan was acquired after each repositioning. For brain studies, the subject's head was fixed with an individually fabricated head holder Tru Scan Image Inc., Annapolis, Md. ; , and serial images were acquired in two bed positions. The timing of the imaging was identical to that described above. Images were acquired with a PC-4096 PET camera Scanditronix AB, Uppsala, Sweden ; , and concentrations of [18F]trovafloxacin in blood were measured with a well counter. The primary imaging parametric values for the PC-4096 camera are in-plane and axial resolutions of a 6.0-mm full width of photopeak measured at half maximum count, 15 contiguous slices at a 6.5-mm separation, and a sensitivity of 5, 000 cps mCi 35 ; . Analytical methods. The PET images were reconstructed by using a conventional filtered back-projection algorithm to an in-plane resolution of a 7-mm full width of photopeak measured at half maximum count. Attenuation correction was performed with transmission images acquired with a rotating pin source containing 68Ge. All projection data were corrected for nonuniformity of detector response, dead time, random coincidences, and scattered radiation. Regions of interest were circular, with a fixed diameter of 16 mm for the myocardium ; . The PET camera was cross-calibrated with a well scintillation counter by comparing the camera response to a uniformly distributed 18F solution in a 20cm-diameter cylindrical phantom with the response of the well counter to an aliquot of the same solution. The concentration of trovafloxacin in each organ expressed as the percentage of injected dose [ID] per gram ; was calculated by dividing the concentration of [18F]trovafloxacin in each tissue determined by PET nanocuries per cubic centimeter ; by the total ID of drug nanocuries ; and multiplying by 100. Since the density of most organs is 1 g cm3, concentrations expressed as percentage of ID per cubic centimeter are approximately equal to concentrations expressed as percentage of ID per gram. For the lung, concentrations were corrected for lung tissue density, 0.26 0.03 g cm3 16 ; . The concentrations of trovafloxacin in the brain were quite low, and radioactivity in the blood made a significant contribution to brain tissue concentrations measured by PET. To correct for this effect, concentrations in brain parenchyma were corrected by subtracting 4% of the concentration of drug in blood from the total tissue concentration. This correction did not have a significant effect on trovafloxacin concentrations in the other tissues. Pharmacokinetic parameters. For each subject, the time dependence of drug concentration percentage of ID per gram ; was tabulated and averaged to yield composite time-concentration curves for each tissue. From the average timeconcentration curves, the following pharmacokinetic parameters were determined in terms of percentage of ID per gram for each tissue: peak concentration, plateau concentration average concentration from 2 to 8 after injection [15] ; , and normalized area under the concentration-time curve AUC ; AUC period of measurement ; . AUCs were calculated by numerical integration by using the trapezoidal rule. It was assumed that the final oral dose of trovafloxacin is completely absorbed, and the pharmacokinetic parameters were converted to absolute concentration units by multiplication by the quotient obtained by dividing the ID by 100. The lowest concentrations of radioactivity that were measured in the present study were approximately 100 nCi cm3, with a precision of 5%. For an ID of mCi, this corresponds to a quantitation limit of 0.001% ID cm3. In terms of absolute drug concentration, this represents a quantification limit of 2.0 g cm3 if 200 mg of unlabeled drug is injected with the tracer. Statistical analysis. The results of the pharmacokinetic studies were evaluated by one-way analysis of variance with a linear model in which organ was the classification variable. Post hoc comparisons of drug concentrations in individual tissues were performed by Duncan's new multiple-range test 7 ; . In order to describe the blood clearance of trovafloxacin in terms of a limited number of parameters, the time dependence of the blood concentration of drug was fit to a biexponential function by a nonlinear least-squares method weighted to variance ; by using the program PROC NLIN SAS Institute ; . All results are expressed as means standard errors of the means SEMs and ursinus.
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Active agent tested against all species except Bacillus spp., which were more susceptible to the fluoroquinolones.When tested against these Gram-positive pathogens from patients with cancer, the spectrum of gatifloxacin was also greater than that of levofloxacin and ciprofloxacin. Gatifloxacin may have a role as part of prophylactic or therapeutic antimicrobial regimens for selected cancer patients with Gram-positive infections. Diekema D.J. et al. Trends in antimicrobial susceptibility of bacterial pathogens isolated from patients with bloodstream infections in the USA, Canada and Latin America. SENTRY Participants Group. Int J Antimicrob Agents. 2000; 13 4 ; : 257-71.p Abstract: From January through June of 1998, 4579 bloodstream infections BSI ; due to bacterial pathogens were reported from SENTRY hospitals in Canada, the USA and Latin America. Staphylococcus aureus, Escherichia coli, and coagulase-negative staphylococcus CoNS ; were the most common pathogens, together accounting for 55.2% of all BSI during this time period. Compared with the 5794 BSI reported from SENTRY from January through June of 1997, no major change was seen in the frequencies of occurrence of the most common bacterial causes of BSI. Between 1997 and 1998, the major change in antimicrobial resistance was an increase in oxacillin-resistance in both S. aureus and CoNS in all regions.These data demonstrate widespread antimicrobial resistance in Canada, Latin America and the USA, with a notable increase in oxacillin-resistance among staphylococci. Ongoing surveillance remains essential, and will enhance efforts to limit the scope of this worldwide problem. Diekema D.J. et al. Survey of bloodstream infections due to gram-negative bacilli: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, and Latin America for the SENTRY Antimicrobial Surveillance Program, 1997. Clin Infect Dis. 1999; 29 3 ; : 595-607.p Abstract: During 1997, a total of 4, 267 nosocomial and community-acquired bloodstream infections due to gram-negative organisms were reported from SENTRY hospitals in Canada 8 sites ; , the United States 30 sites ; , and Latin America 10 sites ; . Escherichia coli was the most common isolate 41% of all gramnegative isolates ; , followed by Klebsiella species 17.9% ; , Pseudomonas aeruginosa 10.6% ; , and Enterobacter species 9.4% ; . For all gram-negative isolates combined, the most active antimicrobials tested were meropenem, imipenem, and cefepime. The quinolones levofloxacin MIC90, 2 microg mL ; , ciprofloxacin MIC90, 1 microg mL ; , gatifloxacin MIC90, 2 microg mL ; , sparfloxacin MIC90, 2 microg mL ; , and trovafloxacin MIC90, 2 microg mL ; were also active against most isolates. Bloodstream infection isolates from Latin America were uniformly more resistant to all classes of antimicrobial agents tested than were isolates from Canada or the United States. Resistance phenotypes consistent with extended-spectrum beta-lactamase production were also most common among E. coli and Klebsiella species from Latin America. Further investigation of the reasons for regional differences in resistance patterns is needed, as is ongoing surveillance to detect resistance trends and to guide antimicrobial use. Digrak M. et al. Antimicrobial activities of several parts of Pinus brutia, Juniperus oxycedrus, Abies cilicia, Cedrus libani and Pinus nigra. Phytother Res. 1999; 13 7 ; : 584-7.p Abstract: In this study, the antimicrobial activities of several parts of various trees grown in the Kahramanmaras region of Turkey were investigated by the disc diffusion method. Chloroform, acetone and methanol extracts of leaves, resins, barks, cones and fruits of Pinus brutia Ten., Juniperus oxycedrus L., Abies cilicia Ant. & Kotschy Carr., Cedrus libani A. Rich. and Pinus nigra Arn. were prepared and tested against Bacillus megaterium DSM 32, Bacillus subtilis IMG 22, Bacillus cereus FMC 19, Escherichia coli DM, Klebsiella pneumoniae FMC 3, Enterobacter aerogenes CCM 2531, Staphylococcus aureus Cowan 1, Mycobacterium smegmatis RUT, Proteus vulgaris FMC 1, Listeria monocytogenes Scoot A, Pseudomonas aeruginosa DSM 5007, Candida albicans CCM 314, Candida tropicalis MDC 86 and.
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GABAY, Y. 1983 ; . Receptors for complement components in inflammation. Agents and Actions 13, 398-405. WIGHT, T . N. 1980 ; . Differences in the synthesis and secretion of sulfated glycosaminoglycans by aorta explant monolayers cultured from atherosclerosis-susceptible and resistant pigeons. Am.J. Path. 101, 127-142 and valcyte.
Pharmaceuticals for distribution by Medicare Plan B providers nationwide. Pharmaceuticals that are manufactured by the Pfizer Group and covered by Medicare Part B include, but may not be limited to, Cerebyx fosphenytoin sodium injection ; , Dilatin phenytoin ; , Diflucan fluconazole ; , Zithromax azithromycin ; , Trovan trovafloxacin mesylate ; , and Unasyn ampicillin sodium sulbactam sodium ; . 115. In addition to manufacturing and marketing drugs that are reimbursed by and trovafloxacin.
5. File, T. M. Jr., Segreti, J., Dunbar, L. et al. 1997 ; . A multicenter, randomized study comparing the efficacy and safety of intravenous and or oral levofloxacin versus ceftriaxone and or cefuroxime axetil in treatment of adults with community-acquired pneumonia. Antimicrob Agents Chemother 41, 196572. 6. Bolmstrom, A., Esberg, K., Wiman, A. et al. 1996 ; . Effects of CO2 incubation on MICs of macrolides? In Programs and Abstracts of the Thirty-sixth Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, LA, 1996, Poster D38, p. 67. American Society for Microbiology, Washington, DC, USA. 7. Konig, C., Simmen, H. P. & Blaser, J. 1993 ; . Effect of pathological changes of pH, and pCO2 on the activity of antimicrobial agents in vitro. Eur J Clin Microbiol Infecti Dis 12, 51926. 8. Malanoski, G. J., Eliopoulos, G. M., Ferraro, M. J. et al. 1993 ; . Effect of pH variation on the susceptibility of Helicobacter pylori to three macrolide antimicrobial agents and temafloxacin. Eur J Clin Microbiol Infect Dis 12, 1313. 9. Johnson, C. C., Livornese, L., Gold, M. J. et al. 1995 ; . Activity of cefepime against ceftazidime-resistant gram-negative bacilli using low and high inocula. J Antimicrob Chemother 35, 76573. 10. Fass, R. J. 1983 ; . In vitro activity of ciprofloxacin Bay o 9867 ; . Antimicrob Agents Chemother 24, 56874. 11. Stearne, L. E., Kooi, C., Goessens, W. H. et al. 2001 ; . In vitro activity of trovafloxacin against Bacteroides fragilis in mixed culture with either Escherichia coli or a vancomycin-resistant strain of Enterococcus faecium determined by an anaerobic time-kill technique. Antimicrob Agents Chemother 45, 24351. 12. Konig, C., Simmen, H. P. & Blaser, J. 1998 ; . Bacterial concentrations in pus and infected peritoneal fluid-implications for bactericidal activity of antibiotics. J Antimicrob Chemother 42, 22732. 13. Soriano, F., Garcia-Corbeira, P., Ponte, C. et al. 1996 ; . Correlation of pharmacodynamic parameters of five beta-lactam antibiotics with therapeutic efficacies in an animal model. Antimicrob Agents Chemother 40, 268690. 14. Chuang, Y. C., Ko, W.C., Wang, S. T. et al. 1998 ; . Minocycline and cefotaxime in the treatment of experimental murine Vibrio vulnificus infection. Antimicrob Agents Chemother 42, 131922. 15. Japan Society of Chemotherapy 1981 ; . Method for the determination of minimum inhibitory concentration MIC ; of aerobic bacteria by agar dilution method. Chemotherapy Tokyo ; 29, 769. 16. Brook, I. 1990 ; . Inoculum effect. Rev Infect Dis 11, 3618. 17. Soriano, F. 1992 ; . Optimal dosage of beta-lactam antibiotics: time above the MIC and inoculum effect. J Antimicrob Chemother 30, 5669. 18. Tsuji, A., Kaneko, Y., Yamaguchi, K. et al. 1994 ; . Correlation between the in vitro and in vivo effects of fourteen beta-lactam compounds in mice with systemic infection. Chemotherapy Basel ; 5, 32432. 19. Craig, W. A. & Gudmundsson, S. 1991 ; . The postantibiotic effect. In Antibiotics in Laboratory Medicine, 2nd edn Lorian, V., Ed. ; , pp. 51536. Williams & Wilkins, Baltimore, MD, USA. 20. Gerber, A. U., Brugger, H. P., Feller, C. et al. 1986 ; . Antibiotic therapy of infections due to Pseudomonas aeruginosa in normal and granulocytopenic mice: comparison of murine and human pharmacokinetics. J Infect Dis 153, 907 21. Bustamante, C. I., Drusano, G. L., Tatem, B. A. et al. 1984 ; . Postantibiotic effect of imipenem on Pseudomonas aeruginosa. Antimicrob Agents Chemother 26, 67882. 22. Nadler, H. L., Pitkin, D. H. & Sheikh, W. 1989 ; . The postantibiotic effect of meropenem and imipenem on selected bacteria. J Antimicrob Chemother 24, Suppl. A, 22531. 23. Kunin, C. M. 1981 ; . Dosage schedules of antimicrobial agents: a historical review. Rev Infect Dis 3, 411. 24. Vogelman, B. S. & Craig, W. A. 1985 ; . Postantibiotic effects. J Antimicrob Chemother 15, Suppl. A, 3746 and valdecoxib.
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