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Dr Ming-Hwa Jong Chief, Department of Hog Cholera Research, Animal Health Research Institute, Council of Agriculture, 376 Chung-Cheng Road, Tanshui, Taipei 25101, TAIPEI CHINA Tel.: 886-2 ; 26.21.21.11 ext. 300 Fax: 886-2 ; 26.22.53.45 E-mail: hc mail.nvri.gov.tw.
Zolid is excreted unchanged in the stool after oral dosing.8, 10 Thus, linezolid may offer an alternative for the treatment of C. difficile-associated diarrhoea CDAD ; . However, serum breakpoints may not be relevant for intraluminal infections. Currently no clinical data are available on the efficacy of linezolid in C. difficile infection. This is the first report of an association between elevated linezolid MICs and high-level resistance to MLSB antimicrobials and fluoroquinolones. Concerning growing resistance against MLSB antimicrobials in C. difficile, the use of linezolid to treat CDAD must be considered cautiously.
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Linezolid is an oxazolidinone antibiotic, first marketed in 2000, which inhibits bacterial protein synthesis in a new and unique way. The drug is active against a range of Gram-positive bacteria, including methicillinresistant and glycopeptide-intermediate ; Staphylococcus aureus, and methicillin-resistant Staphylococcal MRSA ; infection is becoming increasingly common in young children. It is also active against vancomycinresistant enterococci, and strains of Streptocuccus pneumoniae resistant to a range of other antibiotics. It is active against some anaerobes, including Clostridium perfringens, C difficile and Bacteroides fragilis. However Enterobacteriaceae and Pseudomonas aeruginosa are not susceptible to linezolid. Lnezolid is rapidly and completely absorbed when given by mouth, and it penetrates the meninges well when these are inflamed. Thirty per cent is excreted, unchanged, in the urine; the remainder is excreted as inactive metabolites which could accumulate in severe renal failure ; . The half life in children 1 week to 10 years old 23 hours ; is half what it is at birth and in adults. Generally reversible thrombocytopenia can occur when treatment is given for more than 1014 days. More serious temporary marrow depression, similar to that seen with chloramphenicol, has also rarely ; been reported, and a full blood count should probably be performed once a week if sustained treatment becomes necessary. There is also concern that prolonged low dose use could lead to the development of bacterial resistance especially with Enterococcus faecium ; . Linezolid is a weak, reversible, non-selective, monoamine oxidase MAO ; inhibitor, and it has been suggested that this makes use at the same time as or within two weeks of treatment with ; a MAO antidepressant unwise. Similarly, combined use with a range of other antidepressants could cause a "serotonin syndrome" with hyperpyrexia and cognitive dysfunction. No information is available as yet on use during pregnancy, but placental transfer is to be expected, because the drug has a low molecular weight. Indeed, the drug should only be used during pregnancy for the moment when no other good option exists because, although there is no evidence of teratogenicity, increased embryo death, decreased litter size, decreased fetal weight and costal cartilage abnormalities were reported during drug testing in mice. Nothing is known about use during lactation either but, based on extrapolated animal data, a baby might be expected to ingest a little under 10% of the weight-related maternal dose. Manufacturers have not yet recommended use in children under 18.
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655 platelets 45 000 lL. Her blood pressure was 100 50 mm Hg while on an epinephrine infusion. She was intubated and mechanically ventilated and expired on the second hospital day. The reported findings from the autopsy were septic shock with DIC and a skin lesion on the right foot described as an ulcerated lesion 7 8 inch with a central ulcerated area 1 8 inch ; surrounded by contusions. A sample from the lesion was negative for brown recluse spider venom. The postmortem report concluded that death was caused by septic shock and that ba possible spider or insect bite cannot be excluded as the cause of the foot lesion.Q Case 56. A 25-year-old man presented to a remote clinic. Oral ethanol was begun for possible intoxication from ethylene glycol. Further inquiry found that the patient operated a water treatment facility. Search of his home revealed empty packets of aluminum fluoride. The patient's breathing had become more labored, and he was transported to an ED where he was intubated. His vital signs were temperature, 31.18C; blood pressure, 140 80 mm Hg; and heart rate, 110 beats per minute with atrial fibrillation. Laboratory analysis showed potassium, 7.1 mEq L; and serum calcium, 6.7 mg dL. The patient was treated with calcium gluconate, insulin and glucose, and bicarbonate. He died while being resuscitated and awaiting transport to a tertiary medical center. Case 58. A man was riding in a vehicle with a container of anhydrous ammonia for a suspected portable methamphetamine laboratory. The container ruptured. The patient exited the vehicle and ran away from the scene. He was found in cardiac arrest when emergency medical service EMS ; arrived. He was also noted to have second- and thirddegree burns. Despite cardiopulmonary resuscitation CPR ; , the patient expired shortly after arrival at the ED. Case 60. A 26-year-old man fell in his room. He had a history of depression and a previous attempt to harm himself. His mother heard the fall, found him groggy, assumed his symptoms were related to recent sinus problems, and helped him back to bed. A few hours later, he was unresponsive and was brought to the ED with a reported ingestion of cyanide. He was treated with a cyanide antidote kit but remained unresponsive, hypotensive, and acidotic. He was intubated, ventilated, and given dopamine. By 12 hours after arrival, he had no response to stimuli but spontaneously moved and opened his eyes. At 24 hours after admission, he had decorticate posturing. The acidosis resolved, and he was maintaining his blood pressure without vasopressors. The electroencephalogram EEG ; showed general slowing. He died on the second hospital day. Blood cyanide levels were 0.18 lg mL at about 16 hours after arrival at the ED and 0.13 lg mL 10 hours later. Postmortem examination showed bilateral hemorrhagic infarcts of the caudate and putamen of the brain, hypoxic-ischemic encephalopathy, and acute pulmonary thromboemboli. The postmortem heart blood cyanide concentration was 0.27 lg mL and liothyronine.
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| Linezolid 100mg 5mlMeta-analysis Benito E, Obrador A, Stiggelbout A, et al. A population-based case-control study of colorectal cancer in Majorca. I. Dietary factors. Int J Cancer. 1990; 45 1 ; : 69-76. Cohen JH, Kristal AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst. 2000; 92 1 ; : 61-68. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of cruciferous vegetables and prostate cancer. Cancer Epidemiol Biomarkers Prev. 2003; 12 ; : 1403-1409. Graham S, Dayal H, Swanson M, Mittelman A, Wilkinson G. Diet in the epidemiology of cancer of the colon and rectum. J Natl Cancer Inst. 1978; 61 3 ; : 709-714. Hsing AW, McLaughlin JK, Schuman LM, et al. Diet, tobacco use, and fatal prostate cancer: results from the Lutheran Brotherhood Cohort Study. Cancer Res. 1990; 50 21 ; : 6836-6840. J, Allen N, Appleby P, et al. Fruits and vegetables and prostate cancer: no association among 1104 cases in a prospective study of 130544 men in the European Prospective Investigation into Cancer and Nutrition EPIC ; . Int J Cancer. 2004; 109 1 ; : 119-124. Jain MG, Hislop GT, Howe GR, Ghadirian P. Plant foods, antioxidants, and prostate cancer risk: findings from case-control studies in Canada. Nutr Cancer. 1999; 34 2 ; : 173-184. Kojima M, Wakai K, Tamakoshi K, et al. Diet and colorectal cancer mortality: results from the Japan Collaborative Cohort Study. Nutr Cancer. 2004; 50 1 ; : 23-32. Kolonel LN, Hankin JH, Whittemore AS, et al. Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study. Cancer Epidemiol Biomarkers Prev. 2000; 9 8 ; : 795-804. Miller AB, Altenburg HP, Bueno-de-Mesquita B, et al. Fruits and vegetables and lung cancer: Findings from the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2004; 108 2 ; : 269-276.
CARNAHAN: James Carnahan born c1796, d. c1884, s o John Carnahan and Agnes Walker of Kirkcudbrightshire, Scotland: he came to NB in 1816 and settled in Derby, Northumberland County: m. 7 Oct 1824 Jane Cowden ; Gillis born c1798 perhaps at Greenock, Scotland, d. 18 Mar 1880, d o John Cowden and Martha Gibson, and widow of Adam Gillis: Step-children: 1 ; Jennie Gillis born 1821, d. unm. 1 Oct 1902: 2 ; Adam Gillis born c1823, d. 31 May 1896, married 14 Oct 1847 Margaret O'Brien: went to Ellsworth, ME and had issue: Children of James and Jane: 1 ; John Carnahan born c1826, d. 24 Dec 1910, m. 23 Oct 1867 Mary Mowat b. c1828, d. 1891, d o James Mowat and Hannah Clouston: adopted a dau.: 2 ; William Carnahan born c1828, married 29 Jul 1852 Elizabeth Corcoran born 11 Mar 1832 d o George and Jane Corcoran: had seven children: went to Ellsworth, ME in 1860's: 3 ; Mary Carnahan twin ; born 10 Jun 1829, d. 23 Feb 1896, m. 21 Nov 1853 William Corcoran born 28 Jun 1828, died 28 Oct 1906 s o George and Jane Corcoran: had seven children: 4 ; Martha Carnahan twin ; b. 10 Jun 1829, m. 10 Feb 1860 at Derby, Peter Walls born c1839, s o William Howard and Marion Hanna Walls : had three children: 5 ; James Carnahan born 2 Nov 1831, died 15 Jun 1875, married 30 Sep 1855 Margaret Polk born c1835, d. 22 Mar 1885, d o William Polk and Elizabeth Muse: they had ten children: 6 ; Alexander Johnson Carnahan born 13 Apr 1834, died 22 Mar 1885: went to Minnesota: married 13 Apr 1871 Wilhelmina Kepner born 15 Apr 1834, d. 28 Jan 1920: had five children: 7 ; Joseph Carnahan b. c1835: 8 ; Robert Leslie Carnahan born 1 Jun 1837, d. 12 Nov 1907, m. 6 Feb 1872 Mary Ann McGregor b. 27 Apr 1847, died 3 Jan 1919, d o James McGregor and Margaret Caldwell: seven children. Source: MC80 1145 Warren MacKinley's The Carnahan family: James' brother Joseph Carnahan b. 25 Oct 1794, d. unm. 20 Sep 1865, also came to NB and settled in Derby, Northumberland County and lomefloxacin.
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| 1. Mutnick, A. H., Biedenbach, D. J., Turnidge, J. D. & Jones, R. N. 2002 ; . Spectrum and potency evaluation of a new oxazolidinone, linezolid: report from the SENTRY Antimicrobial Surveillance Program, 19982000. Diagnostic Microbiology and Infectious Disease 43, 6573. 2. Ballow, C. H., Jones, R. N., Biedenbach, D. J. & the North American ZAPS Research Group. 2002 ; . A multicenter evaluation of linezolid antimicrobial activity in North America. Diagnostic Microbiology and Infectious Disease 43, 7583. 3. Noskin, G. A., Siddiqui, F., Stosor, V., Hacek, D. & Peterson, L. R. 1999 ; . In vitro activities of linezolid against important Grampositive bacterial pathogens including vancomycin-resistant enterococci. Antimicrobial Agents and Chemotherapy 43, 205962. 4. von Eiff, C. & Peters, G. 1999 ; . Comparative in-vitro activities of moxifloxacin, trovafloxacin, quinupristin dalfopristin and linezolid against staphylococci. Journal of Antimicrobial Chemotherapy 43, 56973. 5. Zurenko, G. E., Yagi, B. H., Schaadt, R. D., Allison, J. W., Kilburn, L. O., Glickman, S. E. et al. 1996 ; . In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents. Antimicrobial Agents and Chemotherapy 40, 83945. 6. Swaney, S. M., Aoki, H., Ganoza, M. C. & Shinabarger, D. L. 1998 ; . The oxazolidinone linezolid inhibits initiation of protein synthesis in bacteria. Antimicrobial Agents and Chemotherapy 42, 32515. 7. Dresser, L. D. & Rybak M. J. 1998 ; . The pharmacologic and bacteriologic properties of oxazolidinones, a new class of synthetic antimicrobials. Pharmacotherapy 18, 45662. 8. Cammarata, S. K., Schueman, L. K., Timm, J. A., Hempsall, K. A., Chang, W., Oliphant, T. H. et al. 2000 ; . Oral linezolid in the treatment of community-acquired pneumonia: a phase III trial. In Program and Abstracts of the American Thoracic Society, Toronto and lomotil.
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Beer's Studies to dateBeers MH et al Explicit criteria for determining inappropriate medication use for nursing home residents, Arch Intern Med 1991; 151: 825-32. Beers MH. Explicit criteria for determining potentially inappropriate medication use by the elderly. An update ibid 1997; 157: 1531-6. Fick DM, Cooper JW, Wade WE, Beers MH et al. Updating the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults Arch Int Med 2003; 163: 2716-24.
Is based on modification of membrane lipids with L-lysine. J. Exp. Med. 193: 10671076. Pillai, S. K., G. Sakoulas, C. Wennersten, G. M. Eliopoulos, R. C. Moellering, Jr., M. J. Ferraro, and H. S. Gold. 2002. Linezolid resistance in Staphylococcus aureus: characterization and stability of resistant phenotype. J. Infect. Dis. 186: 16031607. Ruzin, A., A. Severin, S. L. Moghazeh, J. Etienne, P. A. Bradford, S. J. Projan, and D. M. Shlaes. 2003. Inactivation of mprF affects vancomycin susceptibility in Staphylococcus aureus. Biochim. Biophys. Acta 1621: 117 121. Sader, H. S., T. R. Fritsche, J. M. Streit, and R. N. Jones. 2005. Daptomycin in vitro activity tested against gram-positive strains collected from European and Latin American medical centers in 2003. J. Chemother. 17: 477483. Severinov, K., D. Markov, E. Severinova, V. Nikiforov, R. Landick, S. A. Darst, and A. Goldfarb. 1995. Streptolydigin-resistant mutants in an evolutionarily conserved region of the subunit of Escherichia coli RNA polymerase. J. Biol. Chem. 270: 2392623929. Shinabarger, D. L. 1999. Mechanism of action of the oxazolidinone antibacterial agents. Expert Opin. Investig. Drugs 8: 11951202. Silverman, J. A., N. Oliver, T. Andrew, and T. Li. 2001. Resistance studies with daptomycin. Antimicrob. Agents Chemother. 45: 17991802. Silverman, J. A., N. G. Perlmutter, and H. M. Shapiro. 2003. Correlation of daptomycin bactericidal activity and membrane depolarization in Staphylococcus aureus. Antimicrob. Agents Chemother. 47: 25382544. Stabb, E. V., and J. Handelsman. 1998. Genetic analysis of zwittermicin A and lomustine
Temporary hemodialysis access. Infect. Control Hosp. Epidemiol. 26: 520 524. Cha, R., and M. J. Rybak. 2003. Daptomycin against multiple drug-resistant Staphylococcus and Enterococcus isolates in an in vitro pharmacodynamic model with simulated endocardial vegetations. Diagn. Microbiol. Infect. Dis. 47: 539546. Chatzinikolaou, I., T. F. Zipf, H. Hanna, J. Umphrey, W. M. Roberts, R. Sherertz, R. Hachem, and I. Raad. 2003. lock solution for the prevention of implantable port infections in children with cancer. Clin. Infect. Dis. 36: 116119. Costa, Y., M. Galimand, R. Leclercq, J. Duval, and P. Courvalin. 1993. Characterization of the chromosomal aac 6 ; -Ii gene specific for Enterococcus faecium. Antimicrob. Agents Chemother. 37: 18961903. Costerton, J. W., P. S. Stewart, and E. P. Greenberg. 1999. Bacterial biofilms: a common cause of persistent infections. Science 284: 13181322. Edmond, M. B., J. F. Ober, J. D. Dawson, et al. 1996. Vancomycin-resistant enterococcal bacteremia: natural history and attributable mortality. Clin. Infect. Dis. 23: 12341239. Farber, B. F., M. H. Kaplan, and A. G. Clogston. 1990. Staphylococcus epidermidis extracted slime inhibits the antimicrobial action of glycopeptide antibiotics. J. Infect. Dis. 161: 3740. Fridkin, S. K., C. D. Steward, J. R. Edwards, et al. 1999. Surveillance of antimicrobial use in United States hospitals: project ICARE phase 2. Clin. Infect. Dis. 29: 245252. Golan, Y., D. D. Poutsiaka, S. Tozzi, S. Hadley, S., and D. R. Snydman. 2001. Daptomycin for line-related Leuconostoc bacteraemia. J. Antimicrob. Chemother. 47: 364365. Gray, J., P. J. Marsh, D. Stewart, and S. J. Pedler. 1994. Enterococcal bacteraemia: a prospective study of 125 episodes. J. Hosp. Infect. 27: 179 186. Gristina, A. G. 1987. Biomaterial-centered infection: microbial adhesion versus tissue integration. Science 237: 15881595. Khardori, N., M. Yassien, and K. Wilson. 1995. Tolerance of Staphylococcus epidermidis grown from indwelling vascular catheters to antimicrobial agents. J. Ind. Microbiol. 15: 148151. Kuhn, D. M., T. George, J. Chandra, P. K., Mukherjee, and M. A. Ghannoum. 2002. Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrob. Agents Chemother. 46: 17731780. Lai, K. K. 1996. Treatment of vancomycin-resistant Enterococcus faecium infections. Arch. Intern. Med. 156: 25792584. Leach, T. S., R. Schaser, W. M. Todd, et al. 2000. Clinical efficacy of linezolid for infections caused by vancomycin-resistant enterococci VRE ; in a compassionate use program. Clin. Infect. Dis. 31: 224. Malone, D. A., R. A. Wagner, J. P. Myers, and C. Watanakunakorn. 1986. Enterococcal bacteremia in two large community teaching hospitals. Am. J. Med. 81: 601606. Mermel, L. A., B. M. Farr, R. J. Sherertz, N. O'Grady, J. S. Harris, and D. E. Craven. 2001. Guidelines for the management of intravascular catheterrelated infections. Clin. Infect. Dis. 32: 12491272. Moellering, R. C., P. K. Linden, J., Reinhardt, et al. 1999. The efficacy and safety of Q-D for the treatment of infections caused by vancomycin-resistant Enterococcus faecium. J. Antimicrob. Chemother. 44: 251261. Mohamed, J. A., W. Huang, S. R. Nallapareddy, F. Teng, and B. E. Murray. 2004. Influence of origin isolates, especially endocarditis isolates, and various genes on biofilm formation by Enterococcus faecalis. Infect. Immun. 72: 3658 3663. Montecalvo, M. A., H. Horowitz, C. Gedris, et al. 1994. Outbreak of vancomycin-, ampicillin-, and aminoglycoside-resistant Enterococcus faecium bacteremia in an adult oncology unit. Antimicrob. Agents Chemother. 38: 1363 1367. Morrison, D., N. Woodford, S. P. Barrett, P. Sisson, and B. D. Cookson. 1999. DNA banding pattern polymorphism in vancomycin-resistant Enterococcus faecium and criteria for defining strains. J. Clin. Microbiol. 37: 1084 1091. Murray, B. E., K. V. Singh, J. D. Heath, et al. 1990. Comparison of genomic DNAs of different enterococcal isolates using restriction endonucleases with infrequent recognition sites. J. Clin. Microbiol. 29: 20592063. National Committee for Clinical Laboratory Standards 2002. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7A5. National Committee for Clinical Laboratory Standards, Wayne, Pa. Newell, K. A., J. M. Millis, P. M. Arnow, et al. 1998. Incidence and outcome of infection by vancomycin-resistant Enterococcus following orthotopic liver transplantation. Transplantation 65: 439442. Patterson, J. E., A. H. Sweeney, M. Simms, N. Carley, R. Mangi, J. Sabetta, et al. 1995. An analysis of 110 serious enterococcal infections: Epidemiology, antibiotic susceptibility, and outcome. Medicine Baltimore ; 74: 191200. Raad, I., A. Buzaid, J. Rhyne, R. Hachem, R. Darouiche, H. Safar, M. Albitar, and R. J. Sherertz. 1997. Minocycline and ethylenediaminetetraacetate for the prevention of recurrent vascular catheter infections. Clin. Infect. Dis. 25: 149151.
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Days 7 and 20 were in the photocell dialysis apparatus, and days l-6 were in the home cage.On days 1, 7, and 20 the intraperitoneal dose of cocaine was 15 mp kg, and on days 2-6 it was 30 mg kg. "Basal" refers to studies where dopamine was titrated through the dialysis probe in vim to determine extracellular dopamine content. The number of animals is shown in parentheses. were made between 1 I: 00 and 13: 00 hr. Rats weighing between 260 and 320 gm were anesthetized with Equithesin and mounted in a stereotaxic apparatus David Kopf, Torrance, CA ; . A chronic unilateral dialysis guide cannula 20 gauge stainless steel, 14 mm long ; was implanted 3 mm dorsal to the VTA SN A P 2.6 mm, D V -2.5 mm, M L 0.7 mm: relative to the interaural line according to the atlas of Pellegrino et al., 1979 ; . The cannula was cemented into place by affixing dental acrylic to three stainless steel screws tapped into the skull. The wounds were sutured, and the rats were allowed a minimum of 1 week recovery prior to beginning experimentation. Microdialysis. All microdialysis experiments were conducted as described in the accompanying article Kalivas and DufTy, 1992 ; . The dialysis probes were inserted through the guide cannulas into the VTA SN the night prior to the experiment. The next day, baseline samples 20 min each ; were collected for 60-80 mitt, then cocaine 15.0 mg kg, i.p. ; or saline 1 .O ml kg, i.p. ; was administered and six additional 20 min dialysis samples were obtained. Behavioral data were collected in 20 min intervals simultaneous with the dialysis samples. When the experiment was terminated, the dialysis probe was removed, and the animal returned to its home cage and killed within 7 d for histological verification of the dialysis probe placement see below ; . Treatment groups. Table 1 shows the treatment groups used. Groups 14 were challenged after daily saline or cocaine with acute saline or cocaine injections, while groups 5 and 6 were examined for basal levels ofextracellular dopamine after daily pretreatment with cocaine or saline. The rats were administered either daily saline 1.0 ml kg, i.p. x 6 d; groups 1, 3, and 5 ; or given cocaine 15 mg kg, i.p.; groups 2, 4, and 6 ; on day 1 followed by daily cocaine injections 30 mg kg, i.p. x 5 d ; days 2-6. In groups 1 and 2, the daily saline- and cocaine-pretreated animals were challenged with an acute saline injection 24 hr day 7 ; or 2 weeks day 20 ; after discontinuing the daily treatment regimen. In groups 3 and 4, the rats were challenged with acute cocaine 15 mgkg, i.p. ; on day 7 or day 20. A single dialysis experiment was conducted in each rat; therefore, separate animals were used for each day. In groups 5 and 6 see Table l ; , the basal concentration ofextracellular dopamine was determined by adding dopamine to the dialysis perfusate at concentrations above and below the expected extracellular concentration 0, I, 3, and IO nM ; to generate a series of points that were interpolated to measure the concentration at which no net flux of dopaminc occurred across the dialysis membrane Lonroth et al., 1987; Parsons and Justice, I99 1; Parsons et al., 199 1; see accompanying article, Kalivas and Duffy, 1992 ; . Measurement of dopamine in dialysis samples. The collection of the dialysis samples and quantification of dopamine content were carried out as described in the accompanying article Kalivas and Dully, 1992 ; . Histology and data anal.vsis. Rats were killed with an overdose of pentobarbital, and the location of the dialysis probes in the brain was histologically verified as described in the accompanying article Kalivas and Duffy, 1992 ; . In addition, some tissue sections 50 thick ; were prepared for tyrosine hydroxylase immunocytochemistry as described elsewhere Kalivas and Duffy, 199 1 ; . The neurochemical and behavioral time course data were statistically evaluated using a two-way analysis of variance ANOVA ; with repeated measures over time. Dopamine content was normalized to percentage change from the average of three baseline samples for each experiment prior to statistical analysis. Post hoc evaluation of statistical differences.
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This Phase III study in pediatric patients demonstrated that linezolid was clinically and microbiologically as effective as vancomycin for infections caused by presumed or documented resistant Gram-positive pathogens. The efficacy of linezolid was consistent across all age groups, including neonates, and across the specific site of infection CSSSI, nosocomial pneu and lotronex.
FIG. 1. Antibacterial effects of linezolid means for two replicates per strain ; . A ; MRSA; B ; hVISA; C ; VISA; D ; VRE. E, growth control; OE, 600 mg q12h; 120 mg q12h; , 120-mg 24-h continuous infusion; , 30-mg 24-h continuous infusion and linezolid.
Increasing antibiotic resistance is reported in gram positive pathogens, which are commonly implicated in skin, soft tissue, bone and joint infections. In infections following orthopaedic surgery, isolated staphylococci are reported to be methicillin resistant MRSA ; in up to 50% of cases. Though glycopeptide antibiotics have traditionally been effective in these cases, increasing resistance has been reported and the lack of orally effective preparations has meant long periods of hospitalization for intravenous therapy. Linezolid, the first in a new class of antibiotics, has excellent efficacy against gram positive organisms that are resistant to other therapies and is 100% orally bioavailable. We report early results of its use for the treatment of resistant infections in orthopaedic practice. Analysis of all patients treated with Linezolid in our unit was performed. Infections were characterised according to the UK Nosocomial Infections National Surveillance Service classification of surgical infections as superficial, deep or organ space. We included osteomyelitis, joint sepsis and deep infection involving orthopaedic implants into the final category. Outcome was recorded as clinical, microbiological and blood parameter cure or fail. Over the 12 month study period, 44 patients received linezolid therapy with, 48% had significant co-morbidity. 80% of infections were in association with implanted metal-work. There were 6 cases of septic arthritis, 10 of osteomyelitis and 7 infected joint replacements. All but 2 were treated with vancomycin for a short period before linezolid was used as oral "switch" therapy for longer term administration, allowing early discharge in all cases. MRSA was isolated in 80% of the patients treated. The mean length of Linezolid therapy was 40 days 2-151 ; . Overall, clinical success was achieved in 86%. For superficial, deep and organ spcae infections success rates were 100%, and 77% respectively. Though there were no lifethreatening complications, adverse event rates were significantly higher than those recorded in the literature, with 18% of patients needing to cease therapy. This may be related to the longer duration of therapy compared with previous trials. Linezolid offers an excellent alternative to traditional treatments for resistant infections and can facilitate early discharge. Patients need to be monitored closely, particularly where longterm therapy is planned and lovenox.
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