Download

Yeniden G ndeme Gelen Antibiyotikler






Advertisement
Download Presentation
Comments
josephine
From:
|  
(119) |   (0) |   (0)
Views: 187 | Added: 05-10-2012
Rate Presentation: 1 0
Description:
20. yy\'in ortalari. ?20. y?zyilin ortasini, tarihteki en ?nemli sosyal hastaliklarinin sosyal yasamin ?nemli bir fakt?r? olmaktan ?iktigi an?\"Sir MacFarlane Burnet 1962. ?Simdi Infeksiyon hastaliklari kitabini kapatip, mikroplara karsi savasin kazanildigini ilan etme zamanidir?.\" US Surgeon G
Yeniden G ndeme Gelen Antibiyotikler

An Image/Link below is provided (as is) to

Download Policy: Content on the Website is provided to you AS IS for your information and personal use only and may not be sold or licensed nor shared on other sites. SlideServe reserves the right to change this policy at anytime. While downloading, If for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.











- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -




1. Yeniden G?ndeme Gelen Antibiyotikler Prof.Dr.Iftihar K?KSAL Karadeniz Teknik ?niversitesi Tip Fak?ltesi Infeksiyon Hastaliklari ve Klinik Mikrobiyoloji Anabilim Dali TRABZON

2. 20. yy?in ortalari

3. Can J Infect Dis Med Microbiol. 2005 May?Jun; 16(3): 159?160. Where are all the new antibiotics? The new antibiotic paradox JM Conly, and BL Johnston, 21.yy Bakterilerin yeni diren? ve defans mekanizmalari kesfedildi! Panresistan, XDR mikroorganizmalar! Yeni mikrorganizmalar Yeniden ?nem kazanan eski patojenler Biyoter?rizm tehlikesi Genetik olarak yapilandirilmis patojenler B.anthracis At the beginning of the 20th century, illnesses caused by infectious agents ranked among the most common causes of death in North America and, indeed, worldwide. By the middle of the century, dramatic advances in the diagnosis, management and prevention of infectious diseases had occurred, and hopes were raised that many infectious diseases would be eliminated by the end of the 20th century. Much of this success in the management of infectious diseases was related to a continuous new armamentarium of antibiotics. The discovery of penicillin by Fleming in 1928 followed by the discovery and clinical use of sulphonamides in the 1930s heralded the age of modern antibiotherapy (1,2). These new antibiotics garnered such enthusiasm during the late 1960s and 1970s that some experts believed that infectious diseases would be conquered. Unfortunately, since the early 1990s, humankind has been confronted with an unprecedented number of resurgent and 'new' infectious diseases on a global scale. The threat of bioterrorism, particularly with genetically engineered pathogens such as Bacillus anthracis, has added a new dimension to resurgent infectious diseases, in part because genetic engineering of pathogens could render them resistant to currently available antimicrobials (4,5). It is interesting to note that despite the advances in antimicrobial and vaccine development, infectious diseases still remain as the third-leading cause of death in the United States (6) and the second-leading cause of death worldwide (7). Among the many resurgent and 'new' infectious diseases, antimicrobial resistance represents one of the most significant threats to human health (8-11). The problem of antibiotic resistance, although not new, has increased dramatically during the past 10 to 15 years. It now poses a serious threat to the treatment of infection. Unfortunately, since the early 1990s, humankind has been confronted with an unprecedented number of resurgent and 'new' infectious diseases on a global scale. The threat of bioterrorism, particularly with genetically engineered pathogens such as Bacillus anthracis, has added a new dimension to resurgent infectious diseases, in part because genetic engineering of pathogens could render them resistant to currently available antimicrobials (4,5). It is interesting to note that despite the advances in antimicrobial and vaccine development, infectious diseases still remain as the third-leading cause of death in the United States (6) and the second-leading cause of death worldwide (7). Among the many resurgent and 'new' infectious diseases, antimicrobial resistance represents one of the most significant threats to human health (8-11). The problem of antibiotic resistance, although not new, has increased dramatically during the past 10 to 15 years. It now poses a serious threat to the treatment of infection. At the beginning of the 20th century, illnesses caused by infectious agents ranked among the most common causes of death in North America and, indeed, worldwide. By the middle of the century, dramatic advances in the diagnosis, management and prevention of infectious diseases had occurred, and hopes were raised that many infectious diseases would be eliminated by the end of the 20th century. Much of this success in the management of infectious diseases was related to a continuous new armamentarium of antibiotics. The discovery of penicillin by Fleming in 1928 followed by the discovery and clinical use of sulphonamides in the 1930s heralded the age of modern antibiotherapy (1,2). These new antibiotics garnered such enthusiasm during the late 1960s and 1970s that some experts believed that infectious diseases would be conquered. Unfortunately, since the early 1990s, humankind has been confronted with an unprecedented number of resurgent and 'new' infectious diseases on a global scale. The threat of bioterrorism, particularly with genetically engineered pathogens such as Bacillus anthracis, has added a new dimension to resurgent infectious diseases, in part because genetic engineering of pathogens could render them resistant to currently available antimicrobials (4,5). It is interesting to note that despite the advances in antimicrobial and vaccine development, infectious diseases still remain as the third-leading cause of death in the United States (6) and the second-leading cause of death worldwide (7). Among the many resurgent and 'new' infectious diseases, antimicrobial resistance represents one of the most significant threats to human health (8-11). The problem of antibiotic resistance, although not new, has increased dramatically during the past 10 to 15 years. It now poses a serious threat to the treatment of infection. Unfortunately, since the early 1990s, humankind has been confronted with an unprecedented number of resurgent and 'new' infectious diseases on a global scale. The threat of bioterrorism, particularly with genetically engineered pathogens such as Bacillus anthracis, has added a new dimension to resurgent infectious diseases, in part because genetic engineering of pathogens could render them resistant to currently available antimicrobials (4,5). It is interesting to note that despite the advances in antimicrobial and vaccine development, infectious diseases still remain as the third-leading cause of death in the United States (6) and the second-leading cause of death worldwide (7). Among the many resurgent and 'new' infectious diseases, antimicrobial resistance represents one of the most significant threats to human health (8-11). The problem of antibiotic resistance, although not new, has increased dramatically during the past 10 to 15 years. It now poses a serious threat to the treatment of infection.

4. Diren?li patojenler giderek artiyor! Enterobacteriaceae GSBL AmpC betalaktamazlar Karbapenemazlar Metallobetalaktamazlar MDR Acinetobacter spp

5. Antimikrobiyal ve asi gelismesindeki ilerlemelere ragmen infeksiyon hastaliklari ABD?de 3. t?m d?nyada 2. ?l?m sebebi These new antibiotics garnered such enthusiasm during the late 1960s and 1970s that some experts believed that infectious diseases would be conquered. Unfortunately, since the early 1990s, humankind has been confronted with an unprecedented number of resurgent and 'new' infectious diseases on a global scale. The threat of bioterrorism, particularly with genetically engineered pathogens such as Bacillus anthracis, has added a new dimension to resurgent infectious diseases, in part because genetic engineering of pathogens could render them resistant to currently available antimicrobials (4,5). It is interesting to note that despite the advances in antimicrobial and vaccine development, infectious diseases still remain as the third-leading cause of death in the United States (6) and the second-leading cause of death worldwide (7). Among the many resurgent and 'new' infectious diseases, antimicrobial resistance represents one of the most significant threats to human health (8-11). The problem of antibiotic resistance, although not new, has increased dramatically during the past 10 to 15 years. It now poses a serious threat to the treatment of infection. Unfortunately, since the early 1990s, humankind has been confronted with an unprecedented number of resurgent and 'new' infectious diseases on a global scale. The threat of bioterrorism, particularly with genetically engineered pathogens such as Bacillus anthracis, has added a new dimension to resurgent infectious diseases, in part because genetic engineering of pathogens could render them resistant to currently available antimicrobials (4,5). It is interesting to note that despite the advances in antimicrobial and vaccine development, infectious diseases still remain as the third-leading cause of death in the United States (6) and the second-leading cause of death worldwide (7). Among the many resurgent and 'new' infectious diseases, antimicrobial resistance represents one of the most significant threats to human health (8-11). The problem of antibiotic resistance, although not new, has increased dramatically during the past 10 to 15 years. It now poses a serious threat to the treatment of infection. These new antibiotics garnered such enthusiasm during the late 1960s and 1970s that some experts believed that infectious diseases would be conquered. Unfortunately, since the early 1990s, humankind has been confronted with an unprecedented number of resurgent and 'new' infectious diseases on a global scale. The threat of bioterrorism, particularly with genetically engineered pathogens such as Bacillus anthracis, has added a new dimension to resurgent infectious diseases, in part because genetic engineering of pathogens could render them resistant to currently available antimicrobials (4,5). It is interesting to note that despite the advances in antimicrobial and vaccine development, infectious diseases still remain as the third-leading cause of death in the United States (6) and the second-leading cause of death worldwide (7). Among the many resurgent and 'new' infectious diseases, antimicrobial resistance represents one of the most significant threats to human health (8-11). The problem of antibiotic resistance, although not new, has increased dramatically during the past 10 to 15 years. It now poses a serious threat to the treatment of infection. Unfortunately, since the early 1990s, humankind has been confronted with an unprecedented number of resurgent and 'new' infectious diseases on a global scale. The threat of bioterrorism, particularly with genetically engineered pathogens such as Bacillus anthracis, has added a new dimension to resurgent infectious diseases, in part because genetic engineering of pathogens could render them resistant to currently available antimicrobials (4,5). It is interesting to note that despite the advances in antimicrobial and vaccine development, infectious diseases still remain as the third-leading cause of death in the United States (6) and the second-leading cause of death worldwide (7). Among the many resurgent and 'new' infectious diseases, antimicrobial resistance represents one of the most significant threats to human health (8-11). The problem of antibiotic resistance, although not new, has increased dramatically during the past 10 to 15 years. It now poses a serious threat to the treatment of infection.

6. Despite this increase in antimicrobial resistance, the development of new antimicrobial agents is declining. Several scientific articles, monographs and popular press articles have been published over the past few years pointing out the emerging paradox of a pressing need for new antimicrobial agents juxtaposed against the declining interest in the discovery and introduction of new antimicrobial agents by the world's major pharmaceutical companies. Spellberg et al (12) recently examined the number of new antibacterial agents approved from 1980 to 2003 as well as the number of new antiviral, antifungal and antiparasitic agents approved from 1998 to 2003 by searching United States Food and Drug Administration (FDA) databases. They also examined the research and development programs of 15 major pharmaceutical companies and seven major biotechnology companies via their Internet listings to document trends in the development of new antimicrobial agents. Their findings revealed that FDA approval of new antibacterial agents had decreased by 56% over the past 20 years (1998 to 2002 versus 1983 to 1987). Of the 225 total new entities approved by the FDA from January 1998 to December 2002, only seven (3%) were new antibacterial agents (12). Despite this increase in antimicrobial resistance, the development of new antimicrobial agents is declining. Several scientific articles, monographs and popular press articles have been published over the past few years pointing out the emerging paradox of a pressing need for new antimicrobial agents juxtaposed against the declining interest in the discovery and introduction of new antimicrobial agents by the world's major pharmaceutical companies. Spellberg et al (12) recently examined the number of new antibacterial agents approved from 1980 to 2003 as well as the number of new antiviral, antifungal and antiparasitic agents approved from 1998 to 2003 by searching United States Food and Drug Administration (FDA) databases. They also examined the research and development programs of 15 major pharmaceutical companies and seven major biotechnology companies via their Internet listings to document trends in the development of new antimicrobial agents. Their findings revealed that FDA approval of new antibacterial agents had decreased by 56% over the past 20 years (1998 to 2002 versus 1983 to 1987). Of the 225 total new entities approved by the FDA from January 1998 to December 2002, only seven (3%) were new antibacterial agents (12).

7. Antibiyotik gelistirme

9. Eski antibiyotikler Trimetoprim-sulfametoksazol Klindamisin Tetrasiklin Tigesiklin Polimiksinler Kolistin

10. Trimetoprim-sulfametoksazol CA-MRSA Ilk tanimlama 1980?de

11. Trimetoprim-sulfametoksazol Sulfanamidler CA-MRSA?lara etkili ajanlardir

12. Klindamisin Klindamisin ?ocuklarda toplum k?kenli MRSA ve MSSA infeksiyonlarinin tedavisinde etkilidir

13. Fosfomisin Komplike olmamis ?SI gibi bazi VRE infeksiyonlarinda Linezolid ve quinupristin-dalfopristin?e alternatif Kloramfenikol Genis etki spektrumu, m?kemmel doku penetrasyonu Nedeni bilinmeyen ateste ampirik tedavide Karsit g?r?sler var Kolistin-rifampisin kombinasyonu A. baumannii ve P. aeruginosa infeksiyonlarinda sinerjistik Fusidik asid Stafilokoklara etkili Abstract Multidrug resistant bacteria infections are associated with an increase in attributable mortality and morbidity in ICU patients. Unfortunately, an emerging resistance to novel antibiotics used in the therapy of gram negative and gram positive bacteria infections is often reported in literature. Old antibiotics have been reintroduced in clinical practice. In this review we report the efficacy and safety use of older antimicrobial agents in critically ill patients. Polymyxins are used for nosocomial infection caused by Pseudomonas aeruginosa and Acinetobacter baumannii resistant strains. Patients with polymyxin-only susceptible gram-negative nosocomial pneumonia are reported to be successfully treated with inhaled colistin. Isepamicin can probably be used in intensive care units that harbor Gram-negative bacteria resistant to other aminoglycosides. Fosfomycin may be a useful alternative to linezolid and quinupristin-dalfopristin in the treatment of Vancomycin Resistant Enterococci (VRE) infections in certain clinical situations, e.g. uncomplicated urinary tract infections. Chloramphenicol has a wide antimicrobial spectrum and excellent tissue penetration; though it is sometimes used empirically in the hospital setting for the treatment of patients with unknown source of fever, its role is still a matter of controversy. The colistin/rifampicin combination might have a synergistic effect in Acinetobacter baumannii and Pseudomonas aeruginosa infections. Fusidic acid is active against staphylococcal strains.Abstract Multidrug resistant bacteria infections are associated with an increase in attributable mortality and morbidity in ICU patients. Unfortunately, an emerging resistance to novel antibiotics used in the therapy of gram negative and gram positive bacteria infections is often reported in literature. Old antibiotics have been reintroduced in clinical practice. In this review we report the efficacy and safety use of older antimicrobial agents in critically ill patients. Polymyxins are used for nosocomial infection caused by Pseudomonas aeruginosa and Acinetobacter baumannii resistant strains. Patients with polymyxin-only susceptible gram-negative nosocomial pneumonia are reported to be successfully treated with inhaled colistin. Isepamicin can probably be used in intensive care units that harbor Gram-negative bacteria resistant to other aminoglycosides. Fosfomycin may be a useful alternative to linezolid and quinupristin-dalfopristin in the treatment of Vancomycin Resistant Enterococci (VRE) infections in certain clinical situations, e.g. uncomplicated urinary tract infections. Chloramphenicol has a wide antimicrobial spectrum and excellent tissue penetration; though it is sometimes used empirically in the hospital setting for the treatment of patients with unknown source of fever, its role is still a matter of controversy. The colistin/rifampicin combination might have a synergistic effect in Acinetobacter baumannii and Pseudomonas aeruginosa infections. Fusidic acid is active against staphylococcal strains.

14. Polimiksinler ve Kolistin

15. Polimiksinler Polipeptid antibiyotiklerden Bes farkli kimyasal bilesik (A,B,C,D,E) 1947?de Ingiliz ve Amerikali bilim adamlarinca tanimlandi UK; Bacillus aerosporus- aerosporin (polimiksin A) USA; B.polymyxa- polimiksin (polimiksin D) Polymyxins ? Polymyxins are polypeptide antibiotics that consist of five chemically different compounds (polymyxins A?E). Their mechanism of action includes attachment to the outer cell membrane of Gram-negative bacteria that leads to membrane permeability changes, leakage of cellular contents, and cell death. Most of the drug is excreted unchanged in the urine and, therefore, dose adjustment is required in the setting of renal failure. ? Polymyxins B and, especially, polymyxin E (colistin) are the only ones used in clinical practice. Colistin has been the ?workhorse? in the management of infections caused by MDR (especially carbapenem-resistant) Gram-negative bacteria [5,6??]. It is active against Acinetobacter spp., Pseudomonas aeruginosa, Klebsiella spp., Enterobacter spp., Citrobacter spp., Escherichia coli, Salmonella and Shigella spp., Morganella morganii, and Haemophilus influenzae. It has also considerable activity against Stenotrophomonas spp., but it is not active against Proteus, Providencia and Serratia spp., Burkholderia cepacia, Pseudomonas mallei, Edwardsiella spp., and Brucella spp. Gram-positive cocci and bacilli, Gram-negative cocci and anaerobes are not included in its antimicrobial spectrum. Polymyxins ? Polymyxins are polypeptide antibiotics that consist of five chemically different compounds (polymyxins A?E). Their mechanism of action includes attachment to the outer cell membrane of Gram-negative bacteria that leads to membrane permeability changes, leakage of cellular contents, and cell death. Most of the drug is excreted unchanged in the urine and, therefore, dose adjustment is required in the setting of renal failure. ? Polymyxins B and, especially, polymyxin E (colistin) are the only ones used in clinical practice. Colistin has been the ?workhorse? in the management of infections caused by MDR (especially carbapenem-resistant) Gram-negative bacteria [5,6??]. It is active against Acinetobacter spp., Pseudomonas aeruginosa, Klebsiella spp., Enterobacter spp., Citrobacter spp., Escherichia coli, Salmonella and Shigella spp., Morganella morganii, and Haemophilus influenzae. It has also considerable activity against Stenotrophomonas spp., but it is not active against Proteus, Providencia and Serratia spp., Burkholderia cepacia, Pseudomonas mallei, Edwardsiella spp., and Brucella spp. Gram-positive cocci and bacilli, Gram-negative cocci and anaerobes are not included in its antimicrobial spectrum.

16. Kolistin Polimiksin grubu antibiyotik Polimiksin E Ilk izolasyon 1949?da Japonya?da Bacillus polymyxa var. colistinus?tan 1959?da klinik kullanima giris IM yoldan gram negatif etkinlik It was first isolated in Japan in 1949 from Bacillus polymyxa var. colistinus and became available for clinical use in 1959 [2,3]. Colistin was given as an intramuscular injection for the treatment of gram-negative infections, but fell out of favor after aminoglycosides became available because of its significant side effects. It was later used as topical therapy as part of selective digestive tract decontamination and is still used in aerosolized form for patients with cystic fibrosis. (See "Cystic fibrosis: Antibiotic therapy for lung disease".) It was first isolated in Japan in 1949 from Bacillus polymyxa var. colistinus and became available for clinical use in 1959 [2,3]. Colistin was given as an intramuscular injection for the treatment of gram-negative infections, but fell out of favor after aminoglycosides became available because of its significant side effects. It was later used as topical therapy as part of selective digestive tract decontamination and is still used in aerosolized form for patients with cystic fibrosis. (See "Cystic fibrosis: Antibiotic therapy for lung disease".)

17. Kolistin (Polimiksin E) Tarih?e Ciddi yan etkiler B?brek ve sinir sistemi Topikal kullanim Gastrointestinal sistem dekontaminasyonu (terkedildi) Kistik fibrozlu hastalarda aerosol kullanim 1970?lerde daha az toksik antibiyotikler Kolistin terk edildi

18. Antimikrobiyal diren?; Panresistan bakteri sorunu ?ogul diren?li gram negatiflerde artis Psedomonas aeruginosa Acinetobacter baumannii Klebsiella pneumoniae ?ogul diren?li gram negatiflerle salginlar Salginlar genotipik olarak benzer organizmalarla iliskili olabilir Korunma stratejileri i?in genotip tayini ?nemli

19. Etki Mekanizmasi Bakterinin sitoplazmik membraninda lipopolisakkarit ve fosfolipidlere baglanarak ?sitoplazmik membran? ge?irgenligini degistirir, h?cresel i?erigin bosalmasina ve bakterinin ?l?m?ne yol a?ar

20. Kolistin Iki ticari formu mevcut; Kolistin sulfat; Oral ve topikal Kolistimetat sodyum; Parenteral Her iki form inhalasyon yolu ile de kullanilabilir Kolitsinin iki ticari formu mevcuttur; Oral ve topikal kullanilan kolitsin sulfat ve parenteral kullanilan kolistimetat sodyum. Her iki form inhalasyon yolu ile de kullanilabilir. Kolistin ?ogul diren?li gram negatif infeksiyonlarin tedavisinde kullanilmaktadir.Kolitsinin iki ticari formu mevcuttur; Oral ve topikal kullanilan kolitsin sulfat ve parenteral kullanilan kolistimetat sodyum. Her iki form inhalasyon yolu ile de kullanilabilir. Kolistin ?ogul diren?li gram negatif infeksiyonlarin tedavisinde kullanilmaktadir.

21. Farmakokinetikler- Emilim Kolistimetat sodyum (Kolistin metanesulfonat) ve Kolistin s?lfat gastrointestinal sistemden emilmez Oral veya topikal yolla verildiginde anlamli sekilde absorbe edilmez Kolistin s?lfat barsaklardaki lokal antibakteriyel etki i?in oral yol Kolistimetat sodyum, kolistinin sulfometil derivesi Intraven?z veya intramusk?ler yolla Intratekal yol Inhaler PHARMACOKINETICS???Colistin?is available as both colistin sulfate and colistin methanesulfonate (CMS). Neither form is absorbed from the gastrointestinal tract. CMS is a prodrug that is hydrolyzed after intravenous administration to produce several derivatives, including the active drug colistin. Colistin is tightly bound to membrane lipids of cells of many body tissues, including the liver, lung, kidney, brain, heart, and muscles [27]. Data on the pharmacokinetics of intravenous CMS are sparse [28,29]. CMS has a half-life of 124 minutes, whereas colistin (base) has a half-life of 251 minutes [29]. Colistin has a calculated volume of distribution of 0.34 L/kg [29]. CMS is excreted in the urine. No biliary excretion has been reported in humans. The distribution of colistin?to the pleural cavity, lung parenchyma, bones, and cerebrospinal fluid (CSF) is relatively poor [30,31]. Colistin CSF penetration is low (CSF-to-serum ratio of 5 percent) and bactericidal concentrations are inadequate [32]. Failure of intravenous colistin alone in Acinetobacter ventriculitis has also been reported [33]. However, there are reports of successful treatment with intrathecal colistin for central nervous system infection due to multidrug resistant gram-negative organisms [33-35]. Colistin?penetration into other tissues may be adequate for clinical use in some cases. There are reports of successful treatment of deep prosthetic joint and central nervous system infections with intravenous colistin [4].PHARMACOKINETICS???Colistin?is available as both colistin sulfate and colistin methanesulfonate (CMS). Neither form is absorbed from the gastrointestinal tract. CMS is a prodrug that is hydrolyzed after intravenous administration to produce several derivatives, including the active drug colistin. Colistin is tightly bound to membrane lipids of cells of many body tissues, including the liver, lung, kidney, brain, heart, and muscles [27]. Data on the pharmacokinetics of intravenous CMS are sparse [28,29]. CMS has a half-life of 124 minutes, whereas colistin (base) has a half-life of 251 minutes [29]. Colistin has a calculated volume of distribution of 0.34 L/kg [29]. CMS is excreted in the urine. No biliary excretion has been reported in humans. The distribution of colistin?to the pleural cavity, lung parenchyma, bones, and cerebrospinal fluid (CSF) is relatively poor [30,31]. Colistin CSF penetration is low (CSF-to-serum ratio of 5 percent) and bactericidal concentrations are inadequate [32]. Failure of intravenous colistin alone in Acinetobacter ventriculitis has also been reported [33]. However, there are reports of successful treatment with intrathecal colistin for central nervous system infection due to multidrug resistant gram-negative organisms [33-35]. Colistin?penetration into other tissues may be adequate for clinical use in some cases. There are reports of successful treatment of deep prosthetic joint and central nervous system infections with intravenous colistin [4].

22. Colistimethate is predominantly cleared by the renal route but a fraction of the administered dose is converted in vivo to colistin.33 The colistin formed is mainly cleared by non-renal mechanisms that are as yet not fully characterised. In renal impairment, the elimination of colistimethate by the kidney would be decreased and a greater fraction of the administered dose of colistimethate would be converted to colistin; this explains the need to decrease the dose of colistimethate (sodium) in renally impaired patients who are not receiving renal replacement therapy.28?30 Colistimethate is predominantly cleared by the renal route but a fraction of the administered dose is converted in vivo to colistin.33 The colistin formed is mainly cleared by non-renal mechanisms that are as yet not fully characterised. In renal impairment, the elimination of colistimethate by the kidney would be decreased and a greater fraction of the administered dose of colistimethate would be converted to colistin; this explains the need to decrease the dose of colistimethate (sodium) in renally impaired patients who are not receiving renal replacement therapy.28?30

23. Farmakodinamikler (Ila? ne yapiyor?) 150 mg kolistin IM kullanim : cmax= 5-7 ?g/ml (s?re: 2 saat) IV kullanim : Doruk (pik) serum konsantrasyonlari IM?den daha y?ksektir fakat; ilacin IM kullanimi ile elde edilenden daha hizli d?ser

24. Duyarlilik Testleri Standardize edilmis bir y?ntem yok Tercih edilen y?ntem; Broth mikrodil?syon E test Disk diff?zyon metodu kullanilmamali Agar dil?syon ve Vitek2 kullanilabilir G?venirligi kanitlanmamis There are no standardized methods for colistin?susceptibility testing [17]. The broth microdilution method is preferred for susceptibility testing. E-testing correlates well with broth microdilution at low minimum inhibitory concentrations (MIC between 0.25 and 1 mg/mL) but less reliably at more extreme dilutions [18]. The disk diffusion method cannot be used to test for resistance since polymyxins diffuse poorly in agar [19]. Agar dilution and Vitek2 have also been used, but their reliability is unproven [20-22]. Resistance to colistin?is uncommon. The relative lack of resistance may be at least partially explained by the detergent properties of colistin, which function independently of bacterial metabolic activity [23]. In a surveillance survey of 417 P. aeruginosa strains isolated from cystic fibrosis patients in the United Kingdom, only 13 isolates were resistant to colistin (3 percent) [24]. A second survey of P. aeruginosa isolates from cystic fibrosis patients in Germany found colistin resistance in 5 of 156 mucoid isolates (3.2 percent) and 35 of 229 non-mucoid isolates (15.3 percent) [25].There are no standardized methods for colistin?susceptibility testing [17]. The broth microdilution method is preferred for susceptibility testing. E-testing correlates well with broth microdilution at low minimum inhibitory concentrations (MIC between 0.25 and 1 mg/mL) but less reliably at more extreme dilutions [18]. The disk diffusion method cannot be used to test for resistance since polymyxins diffuse poorly in agar [19]. Agar dilution and Vitek2 have also been used, but their reliability is unproven [20-22]. Resistance to colistin?is uncommon. The relative lack of resistance may be at least partially explained by the detergent properties of colistin, which function independently of bacterial metabolic activity [23]. In a surveillance survey of 417 P. aeruginosa strains isolated from cystic fibrosis patients in the United Kingdom, only 13 isolates were resistant to colistin (3 percent) [24]. A second survey of P. aeruginosa isolates from cystic fibrosis patients in Germany found colistin resistance in 5 of 156 mucoid isolates (3.2 percent) and 35 of 229 non-mucoid isolates (15.3 percent) [25].

25. Kolistin* i?in MIK Breakpointleri

26. Kolistin (50 ?g) i?in Zon ?aplari

27. Kolistin Etki Spektrumu Primer kullanim alani P. aeruginosa A. baumannii infeksiyonlari Etkili oldugu diger patojenler Escherichia coli Bazi Enterobacter spp Klebsiella spp Haemophilus influenzae Bordetella pertussis Legionella pneumophila Salmonella spp Shigella spp Stenotrophomonas maltophilia SPECTRUM OF ACTIVITY???Colistin?has a narrow antibacterial spectrum and is primarily used for infections with P. aeruginosa and A. baumannii. Other susceptible organisms include Escherichia coli, some Enterobacter spp, Haemophilus influenzae, Bordetella pertussis, Legionella pneumophila, Klebsiella spp, Salmonella spp, Shigella spp, and the majority of Stenotrophomonas maltophilia strains (74 percent of 23 tested isolates in one report) [19]. On the other hand, Burkholderia cepacia, Serratia marcescens, Moraxella catarrhalis, Proteus spp, Providencia spp, and Morganella morganii are all resistant to colistin. Other inherently resistant organisms include all gram-positive bacteria and gram-negative cocci. Organisms with variable resistance include Aeromonas, Vibrio, Prevotella, and Fusobacterium spp [3,23,26].SPECTRUM OF ACTIVITY???Colistin?has a narrow antibacterial spectrum and is primarily used for infections with P. aeruginosa and A. baumannii. Other susceptible organisms include Escherichia coli, some Enterobacter spp, Haemophilus influenzae, Bordetella pertussis, Legionella pneumophila, Klebsiella spp, Salmonella spp, Shigella spp, and the majority of Stenotrophomonas maltophilia strains (74 percent of 23 tested isolates in one report) [19]. On the other hand, Burkholderia cepacia, Serratia marcescens, Moraxella catarrhalis, Proteus spp, Providencia spp, and Morganella morganii are all resistant to colistin. Other inherently resistant organisms include all gram-positive bacteria and gram-negative cocci. Organisms with variable resistance include Aeromonas, Vibrio, Prevotella, and Fusobacterium spp [3,23,26].

28. Kolistin Etki Spektrumu Kolistine diren?li patojenler Burkholderia cepacia, Serratia marcescens, Moraxella catarrhalis, Proteus spp, Providencia spp, Morganella morganii Dogal diren?li mikroorganizmalar Gram pozitif bakterilerin ve gram negatif koklarin t?m? Degisken diren?li mikroorganizmalar Aeromonas, Vibrio, Prevotella ve Fusobacterium spp SPECTRUM OF ACTIVITY???Colistin?has a narrow antibacterial spectrum and is primarily used for infections with P. aeruginosa and A. baumannii. Other susceptible organisms include Escherichia coli, some Enterobacter spp, Haemophilus influenzae, Bordetella pertussis, Legionella pneumophila, Klebsiella spp, Salmonella spp, Shigella spp, and the majority of Stenotrophomonas maltophilia strains (74 percent of 23 tested isolates in one report) [19]. On the other hand, Burkholderia cepacia, Serratia marcescens, Moraxella catarrhalis, Proteus spp, Providencia spp, and Morganella morganii are all resistant to colistin. Other inherently resistant organisms include all gram-positive bacteria and gram-negative cocci. Organisms with variable resistance include Aeromonas, Vibrio, Prevotella, and Fusobacterium spp [3,23,26].SPECTRUM OF ACTIVITY???Colistin?has a narrow antibacterial spectrum and is primarily used for infections with P. aeruginosa and A. baumannii. Other susceptible organisms include Escherichia coli, some Enterobacter spp, Haemophilus influenzae, Bordetella pertussis, Legionella pneumophila, Klebsiella spp, Salmonella spp, Shigella spp, and the majority of Stenotrophomonas maltophilia strains (74 percent of 23 tested isolates in one report) [19]. On the other hand, Burkholderia cepacia, Serratia marcescens, Moraxella catarrhalis, Proteus spp, Providencia spp, and Morganella morganii are all resistant to colistin. Other inherently resistant organisms include all gram-positive bacteria and gram-negative cocci. Organisms with variable resistance include Aeromonas, Vibrio, Prevotella, and Fusobacterium spp [3,23,26].

29. Diren? Diren? ?ok nadir ve iyi bilinmez Deterjana benzer olmasi ile a?iklanabilir Bakterinin metabolik aktivitesinden bagimsiz etki Gram negatif bakterilerde mutasyon ya da adaptasyon yolu ile diren? Dis membran degisikligi Dis membran proteinlerinin asiri salinimi Asidik magnezyumdan fakir ortam diren?te ?nemli rol oynar There are no standardized methods for colistin?susceptibility testing [17]. The broth microdilution method is preferred for susceptibility testing. E-testing correlates well with broth microdilution at low minimum inhibitory concentrations (MIC between 0.25 and 1 mg/mL) but less reliably at more extreme dilutions [18]. The disk diffusion method cannot be used to test for resistance since polymyxins diffuse poorly in agar [19]. Agar dilution and Vitek2 have also been used, but their reliability is unproven [20-22]. Resistance to colistin?is uncommon. The relative lack of resistance may be at least partially explained by the detergent properties of colistin, which function independently of bacterial metabolic activity [23]. In a surveillance survey of 417 P. aeruginosa strains isolated from cystic fibrosis patients in the United Kingdom, only 13 isolates were resistant to colistin (3 percent) [24]. A second survey of P. aeruginosa isolates from cystic fibrosis patients in Germany found colistin resistance in 5 of 156 mucoid isolates (3.2 percent) and 35 of 229 non-mucoid isolates (15.3 percent) [25].There are no standardized methods for colistin?susceptibility testing [17]. The broth microdilution method is preferred for susceptibility testing. E-testing correlates well with broth microdilution at low minimum inhibitory concentrations (MIC between 0.25 and 1 mg/mL) but less reliably at more extreme dilutions [18]. The disk diffusion method cannot be used to test for resistance since polymyxins diffuse poorly in agar [19]. Agar dilution and Vitek2 have also been used, but their reliability is unproven [20-22]. Resistance to colistin?is uncommon. The relative lack of resistance may be at least partially explained by the detergent properties of colistin, which function independently of bacterial metabolic activity [23]. In a surveillance survey of 417 P. aeruginosa strains isolated from cystic fibrosis patients in the United Kingdom, only 13 isolates were resistant to colistin (3 percent) [24]. A second survey of P. aeruginosa isolates from cystic fibrosis patients in Germany found colistin resistance in 5 of 156 mucoid isolates (3.2 percent) and 35 of 229 non-mucoid isolates (15.3 percent) [25].

31. Kolistin Klinik kullanim

32. Klinik kullanim Polimiksinler genellikle diger t?m antibiyotiklere diren?li organizmalarin neden oldugu ciddi, hayati tehdit eden gram negatif enfeksiyonlarin tedavisinde kullanilmalidir ?ogul diren?li P.aeruginosa ?ogul diren?li Acinetobacter baumanii ?ogul diren?li K.pneumoniae

33. COLIMYCIN, asagidaki gram negatif organizmalara bagli enfeksiyonlarin tedavisinde klinik olarak etkinligi kanitlanmistir: Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii ve Pseudomonas aeruginosa Bu antibiyotik Proteus veya Neisseria enfeksiyonlarinda kullanilmaz Ilaca diren?li bakteri gelisimini azaltmak ve COLIMYCIN?in ve diger antibakteriyel ila?larin etkinligini saglamak i?in COLIMYCIN, sadece ??oklu dirence sahip bakterilerin? neden olabileceginden s?phelenilen veya kanitlanan enfeksiyonlari tedavi etmek veya ?nlemek i?in kullanilmalidir ENDIKASYONLARI (Prospekt?s)

34. KOLISTIN ile MONOTERAPI ve KOMBINE TEDAVI Kolistin genellikle tek basina da diger antibiyotikler ile kombine olarak da kullanilmakta Kombine kullanildiginda; Bazi antibiyotikler ile sinerjistik etki g?sterdigi Kombinasyon tedavisi kolistine diren? gelisimini engeller Antibiyotik kombinasyonu yapildiginda, Kolistin diren?li suslarda bile bakterisidal etki

35. KOMBINE KULLANILDIGI ANTIBIYOTIKLER Kombine kullaniminda sinerji g?r?len antibiyotikler: 1 Rifampisin Beta laktamlar Amikasin MDR Gram Negatif Trimethoprim/STX bakterilere karsi Siprofloksasin Imipenem Meropenem 2 Tigesiklin

36. Yan etkiler N?rotoksisite ve nefrotoksisite polimiksinlerin en ?nemli iki yan etkisi Nefrotoksisite (%20-25) N?rolojik yan etki (%7-29) Ilacin serum d?zeyi 1-2 ?g/ml?ye ulastiginda y?zde kizarmayla birlikte parestezi, bas d?nmesi, vertigo, ataksi, anlamsiz konusma, uyku hali veya mental konf?zyon N?rotoksisite ve nefrotoksisite polimiksinlerin en ?nemli iki yan etkisidir. Ilacin serum d?zeyi 1-2 ?g/ml?ye ulastiginda y?zde kizarmayla birlikte parestezi, bas d?nmesi, vertigo, ataksi, anlamsiz konusma, uyku hali veya mental konf?zyon g?r?l?r. Polimiksinler ayrica k?rar benzeri etki ile n?romusk?ler iletiyi bloke edebilirler. Uygun tedavi dozunda verildiginde hastalarin yaklasik %20?sinde doz iliskili renal disfonksiyon olusur. Ates ve cilt d?k?nt?leri gibi allerjik reaksiyonlar nadirdir, fakat hizli intraven?z inf?zyon sonrasi sok ve ?rtiker g?r?lm?st?r.N?rotoksisite ve nefrotoksisite polimiksinlerin en ?nemli iki yan etkisidir. Ilacin serum d?zeyi 1-2 ?g/ml?ye ulastiginda y?zde kizarmayla birlikte parestezi, bas d?nmesi, vertigo, ataksi, anlamsiz konusma, uyku hali veya mental konf?zyon g?r?l?r. Polimiksinler ayrica k?rar benzeri etki ile n?romusk?ler iletiyi bloke edebilirler. Uygun tedavi dozunda verildiginde hastalarin yaklasik %20?sinde doz iliskili renal disfonksiyon olusur. Ates ve cilt d?k?nt?leri gibi allerjik reaksiyonlar nadirdir, fakat hizli intraven?z inf?zyon sonrasi sok ve ?rtiker g?r?lm?st?r.

37. Fosfomisin

38. Fosfomisin 1969?da Ispanya?da Streptomyces k?lt?rlerinden elde edildi Uzun yillardir basta ?SI olmak ?zere ?esitli infeksiyonlarin tedavisinde kullanilmakta E. coli suslarinda d?s?k diren? (%1) Ilk kez 1969 yilinda Ispanya?da Streptomyces kulturlerinden elde edilen ve onceleri fosfonomisin olarak adlandirilan fosfomisin trometamol, uzun yillardir basta USE olmak uzere cesitli enfeksiyonlarin tedavisinde kullanilmasina ragmen dunyada Escherichia coli suslarindaki direnc insidansinin son derece dusuk kaldigi (yaklasik %1) nadir antibiyotiklerden biri olma ozelligini tasimaktadir1. Dusuk direnc oranlarina ek olarak fosfomisinin farmakokinetik ve farmakodinamik avantajlari; in vivo aktivitesi ve klinik etkinligi; yuksek duzeyde tolere edilebilir ve guvenilir olmasi gibi dikkate deger ozellikleri de mevcuttur1,2. Bu derleme yazida, yan etki ve bakteriyel direnc gelisim riski daha az olan, tek doz tedavi ile konvansiyonel tedavilerle ayni oranda kur saglayan fosfomisinin farmakolojik ve mikrobiyolojik ozellikleri ile klinik kullanimi tartisilmaktadir.Ilk kez 1969 yilinda Ispanya?da Streptomyces kulturlerinden elde edilen ve onceleri fosfonomisin olarak adlandirilan fosfomisin trometamol, uzun yillardir basta USE olmak uzere cesitli enfeksiyonlarin tedavisinde kullanilmasina ragmen dunyada Escherichia coli suslarindaki direnc insidansinin son derece dusuk kaldigi (yaklasik %1) nadir antibiyotiklerden biri olma ozelligini tasimaktadir1. Dusuk direnc oranlarina ek olarak fosfomisinin farmakokinetik ve farmakodinamik avantajlari; in vivo aktivitesi ve klinik etkinligi; yuksek duzeyde tolere edilebilir ve guvenilir olmasi gibi dikkate deger ozellikleri de mevcuttur1,2. Bu derleme yazida, yan etki ve bakteriyel direnc gelisim riski daha az olan, tek doz tedavi ile konvansiyonel tedavilerle ayni oranda kur saglayan fosfomisinin farmakolojik ve mikrobiyolojik ozellikleri ile klinik kullanimi tartisilmaktadir.

39. Fosfomisin Etki Mekanizmasi Peptidoglikan tabakasinin sentezini engelleyerek In vitro ?alismalarda duyarli bakteriler ?zerinde bakterisidal etkinligini 30 dakika i?inde g?stermekte Bakteri fimbrialarinin sentezini ve hareket yeteneklerini azaltarak hem gram-pozitif hem de gram-negatif ?ropatojenlerin ?riner sistem epitelyumuna ve idrar kateterlerinin i? y?zeyine yapismasini ve kolonizasyonunu engeller Yapilan in vitro calismalarda, fosfomisinin duyarli bakteriler uzerinde bakterisidal etkinligini, 30 dakika icinde gosterdigi ortaya konmustur1,3,5-8. Fosfomisin ayrica, bakteri fimbrialarinin sentezini ve hareket yeteneklerini azaltarak hem gram-pozitif hem de gram-negatif uropatojenlerin uriner sistem epitelyumuna ve idrar kateterlerinin ic yuzeyine yapismasini ve kolonizasyonunu engellemekte, inhibitor konsantrasyonlarin altinda kalsa bile antiadezif etki olusturabilmektedir. Adezif ozellik, bakteriye hucre yuzeyine yapisabilme, idrar akimina karsi koyabilme, mesane yuzeyinde birikebilme ve dokulara girebilme ozelliklerini kazandirmakta; bu ozellik, alt USE patogenezinde anahtar faktor gorevi gormektedir. Fosfomisin, biyofilm tabakalarina gecerek mikroorganizmalar uzerinde etkinligini surdurebilme ozelligine sahiptir. Dusuk inhibitor konsantrasyonlarda bile fosfomisinin, E.coli?nin plazmid transferi yapabilme ve patojenite ile ilgili enzimleri sentezleme yeteneginde zayiflamaya neden oldugu da gosterilmistir1,3,7Yapilan in vitro calismalarda, fosfomisinin duyarli bakteriler uzerinde bakterisidal etkinligini, 30 dakika icinde gosterdigi ortaya konmustur1,3,5-8. Fosfomisin ayrica, bakteri fimbrialarinin sentezini ve hareket yeteneklerini azaltarak hem gram-pozitif hem de gram-negatif uropatojenlerin uriner sistem epitelyumuna ve idrar kateterlerinin ic yuzeyine yapismasini ve kolonizasyonunu engellemekte, inhibitor konsantrasyonlarin altinda kalsa bile antiadezif etki olusturabilmektedir. Adezif ozellik, bakteriye hucre yuzeyine yapisabilme, idrar akimina karsi koyabilme, mesane yuzeyinde birikebilme ve dokulara girebilme ozelliklerini kazandirmakta; bu ozellik, alt USE patogenezinde anahtar faktor gorevi gormektedir. Fosfomisin, biyofilm tabakalarina gecerek mikroorganizmalar uzerinde etkinligini surdurebilme ozelligine sahiptir. Dusuk inhibitor konsantrasyonlarda bile fosfomisinin, E.coli?nin plazmid transferi yapabilme ve patojenite ile ilgili enzimleri sentezleme yeteneginde zayiflamaya neden oldugu da gosterilmistir1,3,7

40. Inhibitor konsantrasyonlarin altinda bile antiadezif etki Adezif ?zellik, bakteriye h?cre y?zeyine yapisabilme, idrar akimina karsi koyabilme, mesane y?zeyinde birikebilme ve dokulara girebilme ?zelliklerini kazandirmakta Biyofilm tabakalarina ge?is ?zelligi D?s?k inhibitor konsantrasyonlarda E.coli?nin plazmid transferi yapabilme ve patojenite ile ilgili enzimleri sentezleme yeteneginde zayiflamaya neden olmakta Yapilan in vitro calismalarda, fosfomisinin duyarli bakteriler uzerinde bakterisidal etkinligini, 30 dakika icinde gosterdigi ortaya konmustur1,3,5-8. Fosfomisin ayrica, bakteri fimbrialarinin sentezini ve hareket yeteneklerini azaltarak hem gram-pozitif hem de gram-negatif uropatojenlerin uriner sistem epitelyumuna ve idrar kateterlerinin ic yuzeyine yapismasini ve kolonizasyonunu engellemekte, inhibitor konsantrasyonlarin altinda kalsa bile antiadezif etki olusturabilmektedir. Adezif ozellik, bakteriye hucre yuzeyine yapisabilme, idrar akimina karsi koyabilme, mesane yuzeyinde birikebilme ve dokulara girebilme ozelliklerini kazandirmakta; bu ozellik, alt USE patogenezinde anahtar faktor gorevi gormektedir. Fosfomisin, biyofilm tabakalarina gecerek mikroorganizmalar uzerinde etkinligini surdurebilme ozelligine sahiptir. Dusuk inhibitor konsantrasyonlarda bile fosfomisinin, E.coli?nin plazmid transferi yapabilme ve patojenite ile ilgili enzimleri sentezleme yeteneginde zayiflamaya neden oldugu da gosterilmistir1,3,7Yapilan in vitro calismalarda, fosfomisinin duyarli bakteriler uzerinde bakterisidal etkinligini, 30 dakika icinde gosterdigi ortaya konmustur1,3,5-8. Fosfomisin ayrica, bakteri fimbrialarinin sentezini ve hareket yeteneklerini azaltarak hem gram-pozitif hem de gram-negatif uropatojenlerin uriner sistem epitelyumuna ve idrar kateterlerinin ic yuzeyine yapismasini ve kolonizasyonunu engellemekte, inhibitor konsantrasyonlarin altinda kalsa bile antiadezif etki olusturabilmektedir. Adezif ozellik, bakteriye hucre yuzeyine yapisabilme, idrar akimina karsi koyabilme, mesane yuzeyinde birikebilme ve dokulara girebilme ozelliklerini kazandirmakta; bu ozellik, alt USE patogenezinde anahtar faktor gorevi gormektedir. Fosfomisin, biyofilm tabakalarina gecerek mikroorganizmalar uzerinde etkinligini surdurebilme ozelligine sahiptir. Dusuk inhibitor konsantrasyonlarda bile fosfomisinin, E.coli?nin plazmid transferi yapabilme ve patojenite ile ilgili enzimleri sentezleme yeteneginde zayiflamaya neden oldugu da gosterilmistir1,3,7

41. Fosfomisin Hizli bakterisidal etkinlik Genis etki spektrumu MRSA Glikopeptid-duyarli ve diren?li enterokoklar, Gram negatif patojenler MDR P.aeruginosa Fosfomycin ? Fosfomycin is an antimetabolite inhibitor of the cytosolic enolpyruvate transferase that prevents the formation of N-acetylmuramic acid, an essential precursor for peptidoglycan chain formation of the bacterial wall. Resistance occurs via decreased intracellular accumulation of the drug. Fosfomycin has a rapid bactericidal effect and a wide antibacterial spectrum, including methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-susceptible or resistant enterococci and a large number of Gram-negative pathogens. ? The concentration of fosfomycin in the soft tissues of healthy volunteers has been shown to be similar to plasma levels. Joukhadar et al. [13] undertook a pharmacokinetics study of nine septic patients to investigate the concentration of fosfomycin in tissue. Drug concentrations in plasma and muscle interstitium exceeded the minimum inhibitory concentrations (MICs) for a number of clinically important pathogens and it was proposed as a useful alternative to other broad-spectrum antibiotics in ICU patients suffering from soft-tissue infections. Surveillance studies have explored the susceptibility of pathogens to fosfomycin in the critical care setting. For example, a 3-year period of surveillance in a German surgical ICU revealed 204 MRSA isolates. Antibiotic susceptibility testing showed that quinolones and gentamicin were also inactive in vitro against MRSA, while 80?100% of the MRSA isolates were susceptible to trimethoprim/sulfamethoxazole, fusidic acid, chloramphenicol, and fosfomycin [14]. Another surveillance study of 210 isolates of P. aeruginosa from patients in eight German ICUs during an observation period of 18 months revealed one outbreak (involving four patients) due to a multidrug resistant strain. This MDR strain of P. aeruginosa was susceptible only to fosfomycin, amikacin, and polymyxin B; the isolates varied in susceptibility to ceftazidime and aztreonam [15]. Fosfomycin ? Fosfomycin is an antimetabolite inhibitor of the cytosolic enolpyruvate transferase that prevents the formation of N-acetylmuramic acid, an essential precursor for peptidoglycan chain formation of the bacterial wall. Resistance occurs via decreased intracellular accumulation of the drug. Fosfomycin has a rapid bactericidal effect and a wide antibacterial spectrum, including methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-susceptible or resistant enterococci and a large number of Gram-negative pathogens. ? The concentration of fosfomycin in the soft tissues of healthy volunteers has been shown to be similar to plasma levels. Joukhadar et al. [13] undertook a pharmacokinetics study of nine septic patients to investigate the concentration of fosfomycin in tissue. Drug concentrations in plasma and muscle interstitium exceeded the minimum inhibitory concentrations (MICs) for a number of clinically important pathogens and it was proposed as a useful alternative to other broad-spectrum antibiotics in ICU patients suffering from soft-tissue infections. Surveillance studies have explored the susceptibility of pathogens to fosfomycin in the critical care setting. For example, a 3-year period of surveillance in a German surgical ICU revealed 204 MRSA isolates. Antibiotic susceptibility testing showed that quinolones and gentamicin were also inactive in vitro against MRSA, while 80?100% of the MRSA isolates were susceptible to trimethoprim/sulfamethoxazole, fusidic acid, chloramphenicol, and fosfomycin [14]. Another surveillance study of 210 isolates of P. aeruginosa from patients in eight German ICUs during an observation period of 18 months revealed one outbreak (involving four patients) due to a multidrug resistant strain. This MDR strain of P. aeruginosa was susceptible only to fosfomycin, amikacin, and polymyxin B; the isolates varied in susceptibility to ceftazidime and aztreonam [15].

42. Fosfomisin klinik kullanim Avrupa ?lkelerinin bir ?ogunda Yumusak doku infeksiyonlari veya sepsis ABD?de FDA ?nerisi Komplike olmamis sistit Cleveland ?alismasi 75 VRE?de fosfomisin duyarliligi %98.7 VRE?de alternatif tedavi Komplike olmamis ?SI Yumusak doku infeksiyonlari MDR gram negatif bakteriler Fosfomycin is occasionally administered for the initial empirical therapy of patients with sepsis or soft-tissue infection in some European countries. In the United States, the Food and Drug Administration has approved fosfomycin only for the treatment of patients with uncomplicated cystitis. Recently, 75 clinical isolates (40 blood and 35 urine isolates) of vancomycin-resistant Enterococcus faecium (VRE) isolated over a year at the Cleveland Clinic were tested for susceptibility to nitrofurantoin, fosfomycin, quinupristin?dalfopristin and linezolid using the E-test. The percentage of isolates susceptible to nitrofurantoin, fosfomycin, quinupristin?dalfopristin and linezolid was 78.7%, 98.7%, 98.7%, and 100%, respectively [17]. Even though this study provides no information about fosfomycin's effect on clinical outcomes, it reaffirms the need to find cheap and atoxic alternatives to linezolid and quinupristin?dalfopristin in the treatment of VRE infections in certain clinical scenarios, for example, uncomplicated urinary tract or soft tissue infections. In addition, we contend that the in-vitro susceptibility of MDR Gram-negative bacteria to fosfomycin and the potential for expanded clinical use of the drug in the current era of increasing antimicrobial resistance deserves to be further investigated. Fosfomycin is occasionally administered for the initial empirical therapy of patients with sepsis or soft-tissue infection in some European countries. In the United States, the Food and Drug Administration has approved fosfomycin only for the treatment of patients with uncomplicated cystitis. Recently, 75 clinical isolates (40 blood and 35 urine isolates) of vancomycin-resistant Enterococcus faecium (VRE) isolated over a year at the Cleveland Clinic were tested for susceptibility to nitrofurantoin, fosfomycin, quinupristin?dalfopristin and linezolid using the E-test. The percentage of isolates susceptible to nitrofurantoin, fosfomycin, quinupristin?dalfopristin and linezolid was 78.7%, 98.7%, 98.7%, and 100%, respectively [17]. Even though this study provides no information about fosfomycin's effect on clinical outcomes, it reaffirms the need to find cheap and atoxic alternatives to linezolid and quinupristin?dalfopristin in the treatment of VRE infections in certain clinical scenarios, for example, uncomplicated urinary tract or soft tissue infections. In addition, we contend that the in-vitro susceptibility of MDR Gram-negative bacteria to fosfomycin and the potential for expanded clinical use of the drug in the current era of increasing antimicrobial resistance deserves to be further investigated.

43. B?brek Yetmezligi Olan Hastalar Ilerlemis b?brek yetmezligi fosfomisinin farmakokinetigi etkiler kreatinin klerensindeki d?smeyle orantili olarak fosfomisinin serum doruk konsantrasyonu ve yarilanma ?mr? artar Renal yetmezligi olan hastalarda (kreatinin klerensi 7-54 ml/dakika) 3 g oral tek doz uygulamasindan sonra fosfomisin trometaminin yarilanma ?mr? 11?den 50 saate kadar uzar idrardan fosfomisinin atilimi yaklasik olarak 2/3 oraninda (%32?den %11?e) azalir Fosfomisin kreatinin klerensi 10 ml/dakika?nin altinda olan kisilerde ve asiri duyarliligi olanlarda kullanilmamali

44. Diger hastalarda kullanim Gebelik kategorisi; B Laktasyon Yenidoganlar Yaslilar Hastane kaynakli bazi yumusak doku infeksiyonlari

45. Fusidik Asit

46. Fusidik Asit ?lkemizde 1998 yilinda kullanima giris Penisilin ve metisilin diren?li stafilokok infeksiyonlarinda kullanim ?nerisi Vankomisin ve teikoplanine alternatif Oral kullanim kolayligi Maliyet etkin ?lkemizde 1998 yilinda kullanima giris Penisilin ve metisilin diren?li stafilokok infeksiyonlarinda kullanim ?nerisi Vankomisin ve teikoplanin gibi glikopeptid antibiyotiklere oral kullanim kolayligi ve maliyet a?isindan alternatif olusturabilen bir antibiyotiktir?lkemizde 1998 yilinda kullanima giris Penisilin ve metisilin diren?li stafilokok infeksiyonlarinda kullanim ?nerisi Vankomisin ve teikoplanin gibi glikopeptid antibiyotiklere oral kullanim kolayligi ve maliyet a?isindan alternatif olusturabilen bir antibiyotiktir

47. Fusidan sinifinin bir ?yesi Fusidium coccineum cinsi mantardan elde edilmistir Kimyasal olarak helvolik asit ve sefalosporin P1 ile yakinlik g?sterir Fusidik asitin sodyum tuzu olan fusidin gelistirilerek 1962 yilinda kullanima sunulmustur Fusidik Asit- Tarih?e Fusidan sinifinin bir ?yesi Fusidium coccineum cinsi mantardan elde edilmistir Kimyasal olarak helvolik asit ve sefalosporin P1 ile yakinlik g?sterir Fusidik asitin sodyum tuzu olan fusidin gelistirilerek 1962 yilinda kullanima sunulmustur. Fusidan sinifinin bir ?yesi Fusidium coccineum cinsi mantardan elde edilmistir Kimyasal olarak helvolik asit ve sefalosporin P1 ile yakinlik g?sterir Fusidik asitin sodyum tuzu olan fusidin gelistirilerek 1962 yilinda kullanima sunulmustur.

48. Fusidik Asit- Etki Mekanizmasi Etki mekanizmasi tam bilinmemekte Protein sentezini inhibe ederek Elongation factor G (EF-G) ve ribozomlar ?zerinden Genellikle bakteriostatik Y?ksek konsantrasyonlarda baktesidal Etki mekanizmasi tam bilinmemekle beraber protein sentezini inhibe ederek etkisini g?sterir. Genellikle bakteriostatik olmasina karsin, y?ksek konsantrasyonlarda baktesidal etki g?sterir. Bakteriyel protein sentezi peptidiltRNA?nin, ribozomun aksept?r b?lgesinden, peptidil b?lgesine translokasyonuna baglidir. Bu olay protein uzatan fakt?r G (protein elangation fakt?r G) ve GTP?nin hidrolizini gerektirir. Fusidik asidin ribozom-uzama fakt?r?- GTP+inorganik fosfor kompleksini stabilize edebildigi d?s?n?lmektedir. Sonu?ta GTP hidrolizi durur ve ribozomda proteinlere aminoasit transferi ger?eklesmez. Etki mekanizmasi tam bilinmemekle beraber protein sentezini inhibe ederek etkisini g?sterir. Genellikle bakteriostatik olmasina karsin, y?ksek konsantrasyonlarda baktesidal etki g?sterir. Bakteriyel protein sentezi peptidiltRNA?nin, ribozomun aksept?r b?lgesinden, peptidil b?lgesine translokasyonuna baglidir. Bu olay protein uzatan fakt?r G (protein elangation fakt?r G) ve GTP?nin hidrolizini gerektirir. Fusidik asidin ribozom-uzama fakt?r?- GTP+inorganik fosfor kompleksini stabilize edebildigi d?s?n?lmektedir. Sonu?ta GTP hidrolizi durur ve ribozomda proteinlere aminoasit transferi ger?eklesmez.

49. Fusidik Asit-Antimikrobiyal Etkinlik ve Diren? Dar spektrumlu ?zellikle MRSA, MRSE suslarina etkin ?-laktamlarla ?apraz diren? g?stermedikleri i?in metisilin diren?li k?kenlerde g?venle kullanilabilirler Etkinlik ?alismalari Bel?ika?da yapilan ?ok merkezli bir ?alismada MRSA suslarinin %90?i i?in fusidik asit MIK degeri 0.06 ?g/ml ve %97?si i?in 0.12 ?g/ml ?lkemizde MRSA, MRSE k?kenlerine karsi fusidik asidin etkinliginin arastirildigi ?alismalarda duyarlilik oranlari MRSA suslarinda %92-100 MSSA suslarinda %98-100 MRSE suslarinda %90-100 MSSE suslarinda %83-100 Fusidik asit dar spektrumludur. ?zellikle metisilin diren?li Staphylococcus aureus ve S.epidermidis (MRSA, MRSE) suslarina etkindir. ?-laktamlarla ?apraz diren? g?stermedikleri i?in metisilin diren?li k?kenlerde g?venle kullanilabilirler. Bel?ika?da yapilan ?ok merkezli bir ?alismada MRSA suslarinin %90?i i?in fusidik asit MIK degeri 0.06 ?g/ml ve %97?si i?in 0.12 ?g/ml bulunmustur. ?lkemizde metisiline duyarli ve diren?li stafilokok k?kenlerine karsi fusidik asidin etkinliginin arastirildigi ?alismalarin sonu?lari da, fusidik asidin stafilokoklar ?zerinde ?ok etkili oldugunu dogrulamaktadir. ?lkemizde yapilan ?alismalarda duyarlik oranlari MRSA suslarinda %92-100, MSSA suslarinda %98-100, MRSE suslarinda%90-100 ve MSSE suslarinda %83-100 olarak bulunmustur. Bu duyarlilik oranlari ile fusidik asit ?zellikle hastane infeksiyonlarinda sik karsilastigimiz MRSA enfeksiyonlarinin tedavisinde glikopeptid antibiyotiklere (vankomisin, teikoplanin) alternatif olusturmakta ve bu infeksiyonlarin dogrudan veya ardisik tedavisinde, tek basina ya da diger antistafilakoksik antibiyotiklerle birlikte kullanilabilmektedir. Fusidik asit dar spektrumludur. ?zellikle metisilin diren?li Staphylococcus aureus ve S.epidermidis (MRSA, MRSE) suslarina etkindir. ?-laktamlarla ?apraz diren? g?stermedikleri i?in metisilin diren?li k?kenlerde g?venle kullanilabilirler. Bel?ika?da yapilan ?ok merkezli bir ?alismada MRSA suslarinin %90?i i?in fusidik asit MIK degeri 0.06 ?g/ml ve %97?si i?in 0.12 ?g/ml bulunmustur. ?lkemizde metisiline duyarli ve diren?li stafilokok k?kenlerine karsi fusidik asidin etkinliginin arastirildigi ?alismalarin sonu?lari da, fusidik asidin stafilokoklar ?zerinde ?ok etkili oldugunu dogrulamaktadir. ?lkemizde yapilan ?alismalarda duyarlik oranlari MRSA suslarinda %92-100, MSSA suslarinda %98-100, MRSE suslarinda%90-100 ve MSSE suslarinda %83-100 olarak bulunmustur. Bu duyarlilik oranlari ile fusidik asit ?zellikle hastane infeksiyonlarinda sik karsilastigimiz MRSA enfeksiyonlarinin tedavisinde glikopeptid antibiyotiklere (vankomisin, teikoplanin) alternatif olusturmakta ve bu infeksiyonlarin dogrudan veya ardisik tedavisinde, tek basina ya da diger antistafilakoksik antibiyotiklerle birlikte kullanilabilmektedir.

50. Fusidik Asit-Antimikrobiyal Etkinlik ve Diren? Hastane infeksiyonlarinda sik karsilasilan MRSA enfeksiyonlarinin tedavisinde glikopeptid antibiyotiklere (vankomisin, teikoplanin) alternatif Dogrudan veya ardisik tedavide tek basina ya da diger antistafilakoksik antibiyotiklerle birlikte kullanilabilmekte Fusidik asit dar spektrumludur. ?zellikle metisilin diren?li Staphylococcus aureus ve S.epidermidis (MRSA, MRSE) suslarina etkindir. ?-laktamlarla ?apraz diren? g?stermedikleri i?in metisilin diren?li k?kenlerde g?venle kullanilabilirler. Bel?ika?da yapilan ?ok merkezli bir ?alismada MRSA suslarinin %90?i i?in fusidik asit MIK degeri 0.06 ?g/ml ve %97?si i?in 0.12 ?g/ml bulunmustur. ?lkemizde metisiline duyarli ve diren?li stafilokok k?kenlerine karsi fusidik asidin etkinliginin arastirildigi ?alismalarin sonu?lari da, fusidik asidin stafilokoklar ?zerinde ?ok etkili oldugunu dogrulamaktadir. ?lkemizde yapilan ?alismalarda duyarlik oranlari MRSA suslarinda %92-100, MSSA suslarinda %98-100, MRSE suslarinda%90-100 ve MSSE suslarinda %83-100 olarak bulunmustur. Bu duyarlilik oranlari ile fusidik asit ?zellikle hastane infeksiyonlarinda sik karsilastigimiz MRSA enfeksiyonlarinin tedavisinde glikopeptid antibiyotiklere (vankomisin, teikoplanin) alternatif olusturmakta ve bu infeksiyonlarin dogrudan veya ardisik tedavisinde, tek basina ya da diger antistafilakoksik antibiyotiklerle birlikte kullanilabilmektedir. Fusidik asit dar spektrumludur. ?zellikle metisilin diren?li Staphylococcus aureus ve S.epidermidis (MRSA, MRSE) suslarina etkindir. ?-laktamlarla ?apraz diren? g?stermedikleri i?in metisilin diren?li k?kenlerde g?venle kullanilabilirler. Bel?ika?da yapilan ?ok merkezli bir ?alismada MRSA suslarinin %90?i i?in fusidik asit MIK degeri 0.06 ?g/ml ve %97?si i?in 0.12 ?g/ml bulunmustur. ?lkemizde metisiline duyarli ve diren?li stafilokok k?kenlerine karsi fusidik asidin etkinliginin arastirildigi ?alismalarin sonu?lari da, fusidik asidin stafilokoklar ?zerinde ?ok etkili oldugunu dogrulamaktadir. ?lkemizde yapilan ?alismalarda duyarlik oranlari MRSA suslarinda %92-100, MSSA suslarinda %98-100, MRSE suslarinda%90-100 ve MSSE suslarinda %83-100 olarak bulunmustur. Bu duyarlilik oranlari ile fusidik asit ?zellikle hastane infeksiyonlarinda sik karsilastigimiz MRSA enfeksiyonlarinin tedavisinde glikopeptid antibiyotiklere (vankomisin, teikoplanin) alternatif olusturmakta ve bu infeksiyonlarin dogrudan veya ardisik tedavisinde, tek basina ya da diger antistafilakoksik antibiyotiklerle birlikte kullanilabilmektedir.

51. Antimikrobiyal Etkinlik ve Diren? Duyarli Gram pozitif koklar MRSA;MRSE; MSSA;MSSE Gram pozitif anaeroblar C. tetani C.difficile C.perfringens Gram negatif anaeroblar Bacteriodes fragilis Bazi gram negatif koklar N. meningitidis, N. gonorrhoeae Nocardia asteroides ve Corynebacterium M. tuberculosis ve M. leprae

52. Diren? farkli mekanizmalar ile olusmakta S.aureus k?kenlerinde kromozomal ya da plazmide bagli Tek ila? kullanimi direnci kolaylastirir Tek ila?ta diren?; %0-2 Kombine tedavide %1?den az Ciddi infeksiyonlarda Fusidik asid+ diger antistafilokoksik antibiyotik kombinasyonlari ?-laktamaz diren?li penisilinler, sefalosporinler, rifampisin Antimikrobiyal Diren?

53. Fusidik Asit-Farmakoloji Oral uygulamadan sonra tama yakin emilim Proteinlere y?ksek oranda (%95-97) baglanir etkin kismi %3-5?lik serbest kismidir Yarilanma ?mr? yaklasik 14-16 saat Proteinlere siki baglandigi i?in t?m doku ve sivilara iyi dagilir Lenfosit, makrofaj ve fibroblast gibi h?crelerin i?ine ge?isi iyi Plasentayi ge?er, anne s?t?nde bulunur Oral uygulamadan sonra emilim tama yakindir. Proteinlere y?ksek oranda (%95-97) baglanir, etkin kismi %3-5?lik serbest kismidir. Yarilanma ?mr? yaklasik 14-16 saattir. Fusidik asit proteinlere siki baglandigi i?in t?m doku ve sivilara iyi dagilir. Lenfosit, makrofaj ve fibroblast gibi h?crelerin i?ine ge?isi de iyidir. Plasentayi ge?er, anne s?t?nde bulunur. Kemik sekestreleri gibi avask?ler infeksiyon odaklarina ge?tigi g?sterilmistir. Kan beyin bariyerini ancak meninkslerin enflamasyonunda ge?ebilir. BOS konsantrasyonu d?s?kt?r ama beyin apselerinde kan konsantrasyonuna yakin ge?is vardir. Fusidik asit karacigerde metabolize edilir ve enterohepatik sirk?lasyona verilir. Fusidik asidin %2?si degismeden diskiya ge?er, %1?i idrarda bulunabilir. B?breklerden atilmadigi i?in renal yetmezliklerde ve hemodiyaliz hastalarinda doz ayarlamasi gerekmez. Karaciger yetmezligi olan hastalarda dikkatli kullanilmalidir. Oral uygulamadan sonra emilim tama yakindir. Proteinlere y?ksek oranda (%95-97) baglanir, etkin kismi %3-5?lik serbest kismidir. Yarilanma ?mr? yaklasik 14-16 saattir. Fusidik asit proteinlere siki baglandigi i?in t?m doku ve sivilara iyi dagilir. Lenfosit, makrofaj ve fibroblast gibi h?crelerin i?ine ge?isi de iyidir. Plasentayi ge?er, anne s?t?nde bulunur. Kemik sekestreleri gibi avask?ler infeksiyon odaklarina ge?tigi g?sterilmistir. Kan beyin bariyerini ancak meninkslerin enflamasyonunda ge?ebilir. BOS konsantrasyonu d?s?kt?r ama beyin apselerinde kan konsantrasyonuna yakin ge?is vardir. Fusidik asit karacigerde metabolize edilir ve enterohepatik sirk?lasyona verilir. Fusidik asidin %2?si degismeden diskiya ge?er, %1?i idrarda bulunabilir. B?breklerden atilmadigi i?in renal yetmezliklerde ve hemodiyaliz hastalarinda doz ayarlamasi gerekmez. Karaciger yetmezligi olan hastalarda dikkatli kullanilmalidir.

54. Fusidik Asit-Endikasyonlar ve Dozlar Akut ve kronik osteomiyelit Septik artrit Endokardit Stafilokoksik endokarditlerde penisilinaz diran?li semisentetik bir penisilin t?revi ile Corynebacteria?larin etlken oldugu endokardit olgularinda ise eritromisin ile birlikte Yumusak doku infeksiyonlari Kistik fibrozlu hastalarda alt solunum yollari infeksiyonlarinin tedavisi MRSA ve MRSE suslarinin etken oldugu infeksiyonlarda glikopeptitlere alternatif Oral kullanim ?st?nl?g? Ucuz maliyeti Uzamis tedavilerinde glikopeptidlerden sonra ardisik olarak C.difficile?ye bagli pseudomembran?z enterokolit Metronidazole alternatif Fusidic acid inhibits bacterial protein synthesis by interacting with a complex of elongation factor G (EF-G) and the ribosome. In the presence of fusidic acid, the release of EF-G GDP from the ribosome is prevented, and consequently, the next stage in translation is blocked. It can be administered topically, intravenously, or, orally with excellent bioavailability. It is highly protein bound, is primarily eliminated by nonrenal mechanisms and has good tissue penetration to skin lesions, burns, infected bone and joints [23]. ? Fusidic acid is active in vitro only against Gram-positive bacteria, such as various strains of staphylococci, including methicillin-susceptible, methicillin-resistant and even vancomycin-intermediate strains of S. aureus (VISA), and most coagulase-negative staphylococci [24??]. Of note, fusidic acid has only limited activity against streptococci and enterococci. The action of fusidic acid is mainly bacteriostatic but, at high concentrations, it may be bactericidal. Alteration of the target protein EF-G is the major mechanism of resistance. ? Fusidic acid is usually used in combination with another antistaphylococcal antibiotic to decrease the emergence of resistance. It is used mainly in combination with rifampin, [beta]-lactams or vancomycin for the treatment of staphylococcal bacteremia, endocarditis, soft-tissue infections (including those following burns), and bone/joint infections [25?27]. It should be noted that in-vitro antagonism between fusidic acid and quinolones has been reported [28]. There is a dearth of data regarding the effectiveness and safety of fusidic acid for the treatment of critically ill patients with infection. In a recent study [27] of 25 patients (including nine ICU patients) with serious infections (e.g. endocarditis and bacteremia) due to MRSA with reduced susceptibility to vancomycin, 12 patients received a combination of rifampin and fusidic acid. The use of fusidic acid in the treatment of mild or severe staphylococcal infections may obviate the need to use daptomycin or oxazolidinones and, probably, delay the inevitable development of resistance to these agents. Finally, it should be noted that fusidic acid has been used as an alternative to metronidazole in the treatment of the initial episode of pseudomembranous colitis [29]. Fusidic acid inhibits bacterial protein synthesis by interacting with a complex of elongation factor G (EF-G) and the ribosome. In the presence of fusidic acid, the release of EF-G GDP from the ribosome is prevented, and consequently, the next stage in translation is blocked. It can be administered topically, intravenously, or, orally with excellent bioavailability. It is highly protein bound, is primarily eliminated by nonrenal mechanisms and has good tissue penetration to skin lesions, burns, infected bone and joints [23]. ? Fusidic acid is active in vitro only against Gram-positive bacteria, such as various strains of staphylococci, including methicillin-susceptible, methicillin-resistant and even vancomycin-intermediate strains of S. aureus (VISA), and most coagulase-negative staphylococci [24??]. Of note, fusidic acid has only limited activity against streptococci and enterococci. The action of fusidic acid is mainly bacteriostatic but, at high concentrations, it may be bactericidal. Alteration of the target protein EF-G is the major mechanism of resistance. ? Fusidic acid is usually used in combination with another antistaphylococcal antibiotic to decrease the emergence of resistance. It is used mainly in combination with rifampin, [beta]-lactams or vancomycin for the treatment of staphylococcal bacteremia, endocarditis, soft-tissue infections (including those following burns), and bone/joint infections [25?27]. It should be noted that in-vitro antagonism between fusidic acid and quinolones has been reported [28]. There is a dearth of data regarding the effectiveness and safety of fusidic acid for the treatment of critically ill patients with infection. In a recent study [27] of 25 patients (including nine ICU patients) with serious infections (e.g. endocarditis and bacteremia) due to MRSA with reduced susceptibility to vancomycin, 12 patients received a combination of rifampin and fusidic acid. The use of fusidic acid in the treatment of mild or severe staphylococcal infections may obviate the need to use daptomycin or oxazolidinones and, probably, delay the inevitable development of resistance to these agents. Finally, it should be noted that fusidic acid has been used as an alternative to metronidazole in the treatment of the initial episode of pseudomembranous colitis [29].

56. Beta-laktamazlar nasil etki g?sterir? Beta-laktamazlar etkilerini antibiyotik molek?l?n?n beta-laktam halkas?n? hidrolize u?ratarak ?k?rmak? yoluyla g?sterirler. Bu ?ekilde hidrolize u?rayan beta-laktam molek?l? inaktif hale ge?er. Beta-laktamazlar nasil etki g?sterir? Beta-laktamazlar etkilerini antibiyotik molek?l?n?n beta-laktam halkas?n? hidrolize u?ratarak ?k?rmak? yoluyla g?sterirler. Bu ?ekilde hidrolize u?rayan beta-laktam molek?l? inaktif hale ge?er.

57. Endikasyonlari Belirli antibiyotiklerle kombine edilerek orta ila agir dereceli bakteriyel enfeksiyonlarin tedavisinde kullanilir Kombine antibiyotik kullanimi beta laktam antibiyotiklerinin tek basina uygulanmasina tercih edilir daha y?ksek terap?tik g?vence

58. Kullanim Beta laktamazlarin ?ogunu inhibe eder AmpC sefalosporinazlara etkisiz Pseudomonas aeruginosa Citrobacter Enterobacter Serratia Avrupa ve ABD?de kombine preparatlar cefoperazone/sulbactam ve ampicillin/sulbactam

59. Ampisilin-sulbaktam etki spektrumu Streptococci, enterococci Listeria spp., S. aureus H. influenzae (B-lakt ?retenler) E. coli, P. mirabilis Salmonella spp., ve Shigella spp. M. catarrhalis, E. coli Proteus spp., Klebsiella spp. Anaeroblar

60. Ampisilin-sulbaktam Kombinasyon 2 g ampisilin-1 g sulbaktam Polimikrobiyal infeksiyonlar Abdominal ve jinekolojik cerrahi inf.lar Aspirasyon pn?monisi Odontojenik abseler Diyabetik ayak inf.lari E. coli ?de ampisillin-sulbaktam direnci!! Sulbaktam oral yoldan iyi emilmez, parenteral verilmelidir

61. Sefoperazon sodyum-sulbaktam SBT/CPZ (1000 mg + 1000 mg)(1:1) Etki spektrumu Gram pozitifler Gram negatiflaer Anaeroblar

62. Diger kombinasyonlar

63. Seftazidim + sulbaktam E.clocae, A.baumannii, GSBL(+) K.pneumoniae Imipenem + sulbaktam Acinetobacter spp ( imipenem R suslar ) Sefepim + sulbaktam Acinetobacter spp ( imipenem R suslar ) Sefotaksim + sulbaktam E.clocae, S.marcescens, A.baumannii, GSBL (+) K.penumoniae Aztreonam + sulbaktam E.clocae, imipenem S ve R A.baumannii, GSBL E.coli Sulbaktam beta laktamlarin diren?li pek ?ok diren?li gram negatif aktivitesini arttiriyor.Sulbaktam beta laktamlarin diren?li pek ?ok diren?li gram negatif aktivitesini arttiriyor.

64. Amoksisilin-sulbaktam Ama? Amoksisilin-sulbaktamin in vitro etkinligini degerlendirmek (agar dil?syon ile) Karsilastirma ila?lari Amoksisilin, Ampisilin-sulbaktam, amoksisilin-klavulonat, sefotaksim Sonu?lar Amoksisilin-sulbaktam gram pozitiflerde %90.9 etkili E.coli %82.4 Klebsiella %83 H. Influenzae %100 Acinetobacter %83.3 Yorum Amoksisilin-sulbaktam basta Acinetobacter olmak ?zere etkili bir antibiyotiktir Aim To evaluate the antibacterial activity of Amoxicillin sulbactam compared with other four antimicrobial agents in vitro.Methods Amoxicillin sulbactam against clinical isolated strains were compared with amoxicillin,ampicillin sulbactam ,amoxicillin clavulanic acid and cefetaxime.Minimal Inhibitory Concentrations (MIC) were determined by use of agar dilution method.Results The susceptible rate of amoxicillin sulbactam against gram positive ball strains was 90.91%,higher than those of amoxicillin and cefetaxime.The susceptible rate of amoxicillin sulbactam against E.coli,Klebsiella pneumoniae and Hamophilas influenzae was 82.35% 83.3% and 100%,similar with those of amoxicillin clavulanic acid,ampicillin sulbactam and cefetaxime,higher than that of amoxicillin.The susceptible rate of amoxicillin sulbactam against Acinetobacter was 83.33%,higher than that of amoxicillin significantly,and better than other two agents containing ?-lactamases inhibitors and cefetaxime.The antibacterial activity of amoxicillin sulbactam against common clinical isolates was better than that of amoxicillin,especially to ?-lactamases positive strains.Conclusion Amoxicillin sulbactam is an effective antibiotic containing ?-lactamases inhibitor and a powerful antimicrobial agents for clinical bacterial infection,especially to Acinetobacter. Aim To evaluate the antibacterial activity of Amoxicillin sulbactam compared with other four antimicrobial agents in vitro.Methods Amoxicillin sulbactam against clinical isolated strains were compared with amoxicillin,ampicillin sulbactam ,amoxicillin clavulanic acid and cefetaxime.Minimal Inhibitory Concentrations (MIC) were determined by use of agar dilution method.Results The susceptible rate of amoxicillin sulbactam against gram positive ball strains was 90.91%,higher than those of amoxicillin and cefetaxime.The susceptible rate of amoxicillin sulbactam against E.coli,Klebsiella pneumoniae and Hamophilas influenzae was 82.35% 83.3% and 100%,similar with those of amoxicillin clavulanic acid,ampicillin sulbactam and cefetaxime,higher than that of amoxicillin.The susceptible rate of amoxicillin sulbactam against Acinetobacter was 83.33%,higher than that of amoxicillin significantly,and better than other two agents containing ?-lactamases inhibitors and cefetaxime.The antibacterial activity of amoxicillin sulbactam against common clinical isolates was better than that of amoxicillin,especially to ?-lactamases positive strains.Conclusion Amoxicillin sulbactam is an effective antibiotic containing ?-lactamases inhibitor and a powerful antimicrobial agents for clinical bacterial infection,especially to Acinetobacter.

65. Seftriakson-sulbaktam

66. Sefepim-sulbaktam ? Cefepime 500mg, sulbactam 250mg ? Cefepime 1000mg, sulbactam 500mg ? Cefepime 2000mg, sulbactam 1000mg

67. Acinetobacter baumannii Sulbaktamin direkt antibakteriyel etkisi ?ok ?nemli Karbapenem S/R(farketmez) + sulbaktam (sinerjik etki) Sefepim/seftazidim kullaniliyorsa mutlaka sulbaktam eklenmeli PER-1 sorunu %20-40 Kolistin kullaniliyorsa sulbaktamla kombine edilebilir kolistin direncinin engellenmesi

69. Sulbaktam ve gebelik Gebelik kategorisi :B Anne s?t?nde sulbaktam konsantrasyonu ortalama 0.5 ?g/mL gibi olduk?a d?s?k miktarda diger beta-laktam antibiyotiklere benzer Beta-laktam antibiyotiklerle birlikte veya tek basina postpartum d?nemdeki infeksiyonlarin tedavisinde g?venle kullanilabilir

70. Sulbaktam uygun endikasyon ?neriler Polimikrobiyal infeksiyonlarda ikinci-d?rd?nc? kusak sefalosporinlerle Toplum k?kenli orta ve siddetli infeksiyonlarda Hastane k?kenli orta siddette infeksiyonlarda Olasi bir stafilokoksik infeksiyonun ampirik tedavisinde birinci kusak sefalosporinlere sulbaktam ilavesi Toplum k?kenli orta veya siddetli infeksiyonlarda Hastane k?kenli orta siddette infeksiyonlarda

71. 3. Enterik bakterilerin etken olmasi beklenen infeksiyonlarinda ???nc? ve d?rd?nc? kusak sefalosporinlerle sulbaktam kombinasyonu Toplum k?kenli siddetli infeksiyonlarda Hastane k?kenli orta siddetli infeksiyonlarda 4. GSBL ?reten enterik bakteriler in vitro testlerde beta-laktam/beta-laktamaz inhibit?r? kombinasyonlarina duyarli saptandiysa sulbaktamli beta-laktam kombinasyonu kullanimi degerlendirilebilir Sulbaktam uygun endikasyon ?neriler

72. Acinetobacter baumannii tek ya da kombinasyon Anaerobik infeksiyonlar tek (?) ya da kombinasyon Sulbaktam uygun endikasyon ?neriler

73. Isepamisin Gentamisin B derivesi, amikasine benzer ?zellikler? Zenginlestirilmis etki Enterobacteriaceae ve stafilokoklar The Belgian Isepamicin Multicenter Study Group ?alismasi YB? hastalarindan1100 gram negatif izolat Duyarliliklar Isepamisin %91 meropenem %94 sefepim ve amikasin %89 gentamisin %88 Siprofloksasin %84 Isepamicin ? Isepamicin is an aminoglycoside derived from gentamicin B with properties similar to those of amikacin, but with enhanced activity against isolates producing type I 6'-acetyltransferase. Its antibacterial spectrum includes Enterobacteriaceae and staphylococci. In France, isepamicin's pharmacokinetic characteristics have been studied extensively in the specific population of ICU patients [18,19]. For example, in a study of approximately 200 ICU patients treated for nosocomial pneumonia with isepamicin and a [beta]-lactam antibiotic, isepamicin's clearance was found to be related to age, body weight and serum creatinine level, while it was independent of the dosage (15 versus 25 mg/kg) and the duration of treatment (5 versus 10 days). The authors suggested that individual therapeutic drug monitoring seems unnecessary in the critical care setting if the medication is used in a manner similar to the one described in their study. The Belgian Isepamicin Multicenter Study Group ?alismasi compared the in-vitro activity of isepamicin with that of meropenem, cefepime, amikacin, gentamicin, and ciprofloxacin against approximately 1100 Gram-negative isolates (Enterobacteriaceae and nonfermenting Gram-negative bacteria) recovered from ICU patients of 11 Belgian hospitals [20]. Overall, isepamicin was active against 91% of all isolates; it was less active than meropenem (94% susceptibility) but more active than cefepime and amikacin (89% susceptibility), gentamicin (88% susceptibility), and ciprofloxacin (84% susceptibility). Compared with amikacin, MIC values for isepamicin were usually two to four-fold lower for most Enterobacteriaceae, while they were similar for P. aeruginosa and other nonfermenters. More than 95% of all tested isolates showed similar profiles of resistance/susceptibility against both isepamicin and amikacin. Nonetheless, 12% of Enterobacter aerogenes isolates were susceptible to isepamicin and resistant to amikacin while 6% of P. aeruginosa isolates were intermediate/resistant to isepamicin and intermediate/susceptible to amikacin. The authors considered isepamicin ?as a suitable agent for empiric therapeutic use in severe ICU-acquired Gram-negative infections in Belgium?. Isepamicin ? Isepamicin is an aminoglycoside derived from gentamicin B with properties similar to those of amikacin, but with enhanced activity against isolates producing type I 6'-acetyltransferase. Its antibacterial spectrum includes Enterobacteriaceae and staphylococci. In France, isepamicin's pharmacokinetic characteristics have been studied extensively in the specific population of ICU patients [18,19]. For example, in a study of approximately 200 ICU patients treated for nosocomial pneumonia with isepamicin and a [beta]-lactam antibiotic, isepamicin's clearance was found to be related to age, body weight and serum creatinine level, while it was independent of the dosage (15 versus 25 mg/kg) and the duration of treatment (5 versus 10 days). The authors suggested that individual therapeutic drug monitoring seems unnecessary in the critical care setting if the medication is used in a manner similar to the one described in their study. The Belgian Isepamicin Multicenter Study Group ?alismasi compared the in-vitro activity of isepamicin with that of meropenem, cefepime, amikacin, gentamicin, and ciprofloxacin against approximately 1100 Gram-negative isolates (Enterobacteriaceae and nonfermenting Gram-negative bacteria) recovered from ICU patients of 11 Belgian hospitals [20]. Overall, isepamicin was active against 91% of all isolates; it was less active than meropenem (94% susceptibility) but more active than cefepime and amikacin (89% susceptibility), gentamicin (88% susceptibility), and ciprofloxacin (84% susceptibility). Compared with amikacin, MIC values for isepamicin were usually two to four-fold lower for most Enterobacteriaceae, while they were similar for P. aeruginosa and other nonfermenters. More than 95% of all tested isolates showed similar profiles of resistance/susceptibility against both isepamicin and amikacin. Nonetheless, 12% of Enterobacter aerogenes isolates were susceptible to isepamicin and resistant to amikacin while 6% of P. aeruginosa isolates were intermediate/resistant to isepamicin and intermediate/susceptible to amikacin. The authors considered isepamicin ?as a suitable agent for empiric therapeutic use in severe ICU-acquired Gram-negative infections in Belgium?.

74. Kloramfenikol Protein sentezini bakteri ribozomunun 50S subuniti ?zerinden inhibe eder Genellikle bakteriyostatiktir Bazi bakteriler i?in bakterisidaldir S. pneumoniae, N. meningitidis, ve H. influenzae Genis spektrumlu Gram pozitif ve negatifler Anaeroblar Spiroketler, Riketsiya, Klamidia ve Mikoplazma Parenteral ve oral yoldan etkili Oral biyoyararlanimi %80 M?kemmel doku konsantrasyonu Chloramphenicol ? Chloramphenicol inhibits protein synthesis by binding reversibly to the 50 S subunit of the bacterial ribosome. Chloramphenicol is generally bacteriostatic, but may be bactericidal in high concentrations or when used against highly susceptible bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Hemophilus influenzae. Its spectrum of activity is broad, including Gram-positive and Gram-negative bacteria, anaerobes, spirochetes, rickettsiae, chlamydiae, and mycoplasma. It is effective parenterally as well as orally (bioavailability 80%) and has excellent tissue penetration. Chloramphenicol is metabolized primarily in the liver, where it is conjugated and excreted in an inactive form by the kidneys. Dose adjustment is required in hepatic, but not renal, insufficiency. Bacteria may develop resistance to chloramphenicol by decreasing their membrane permeability to the drug or by producing an inactivating enzyme, chloramphenicol acetyltransferase. Bone marrow suppression is the most significant adverse effect and may even take the form of a fatal idiosyncratic aplastic anemia. ? Chloramphenicol is still used extensively in Africa and Southeast Asia in the treatment of critically ill patients with bacterial meningitis, brain abscess, melioidosis, rickettsial infections and typhoid fever. In the developed world it is still used occasionally for the treatment of severe infections (e.g. in a case of Stenotrophomonas maltophilia endocarditis of a prosthetic aortic valve in combination with ciprofloxacin [30]) and it may become a useful agent in the treatment of MDR organisms such as VRE or MRSA. In a study of 78 episodes of VRE bacteremia in an academic medical center (including 46 patients located in the ICU) chloramphenicol treatment led to a favorable clinical and microbiological response of approximately 60% and 80%, respectively. Even though hematological abnormalities were noted in one-third of the patients, none could be directly linked to chloramphenicol use [31]. Chloramphenicol has also been administered to treat nosocomial VRE infections in liver transplant recipients [32]. Recently, the successful combined intravenous and intraventricular chloramphenicol treatment of a critically ill patient with subarachnoid hemorrhage and meningitis due to VRE was reported [33]. Of interest, chloramphenicol has also been used successfully for the treatment of VRE infections in a thermal injury patient that developed resistance to quinupristin?dalfopristin [34]. ? Finally, it should be noted that due to its wide antimicrobial spectrum and excellent tissue penetration, chloramphenicol is used sometimes empirically in the hospital setting for the treatment of patients with unknown source of fever. This treatment, however, cannot be widely recommended as it is based on anecdotal experience. Further studies are needed to better define the role of chloramphenicol in the modern treatment of infections of critically ill patients. ?Chloramphenicol ? Chloramphenicol inhibits protein synthesis by binding reversibly to the 50 S subunit of the bacterial ribosome. Chloramphenicol is generally bacteriostatic, but may be bactericidal in high concentrations or when used against highly susceptible bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Hemophilus influenzae. Its spectrum of activity is broad, including Gram-positive and Gram-negative bacteria, anaerobes, spirochetes, rickettsiae, chlamydiae, and mycoplasma. It is effective parenterally as well as orally (bioavailability 80%) and has excellent tissue penetration. Chloramphenicol is metabolized primarily in the liver, where it is conjugated and excreted in an inactive form by the kidneys. Dose adjustment is required in hepatic, but not renal, insufficiency. Bacteria may develop resistance to chloramphenicol by decreasing their membrane permeability to the drug or by producing an inactivating enzyme, chloramphenicol acetyltransferase. Bone marrow suppression is the most significant adverse effect and may even take the form of a fatal idiosyncratic aplastic anemia. ? Chloramphenicol is still used extensively in Africa and Southeast Asia in the treatment of critically ill patients with bacterial meningitis, brain abscess, melioidosis, rickettsial infections and typhoid fever. In the developed world it is still used occasionally for the treatment of severe infections (e.g. in a case of Stenotrophomonas maltophilia endocarditis of a prosthetic aortic valve in combination with ciprofloxacin [30]) and it may become a useful agent in the treatment of MDR organisms such as VRE or MRSA. In a study of 78 episodes of VRE bacteremia in an academic medical center (including 46 patients located in the ICU) chloramphenicol treatment led to a favorable clinical and microbiological response of approximately 60% and 80%, respectively. Even though hematological abnormalities were noted in one-third of the patients, none could be directly linked to chloramphenicol use [31]. Chloramphenicol has also been administered to treat nosocomial VRE infections in liver transplant recipients [32]. Recently, the successful combined intravenous and intraventricular chloramphenicol treatment of a critically ill patient with subarachnoid hemorrhage and meningitis due to VRE was reported [33]. Of interest, chloramphenicol has also been used successfully for the treatment of VRE infections in a thermal injury patient that developed resistance to quinupristin?dalfopristin [34]. ? Finally, it should be noted that due to its wide antimicrobial spectrum and excellent tissue penetration, chloramphenicol is used sometimes empirically in the hospital setting for the treatment of patients with unknown source of fever. This treatment, however, cannot be widely recommended as it is based on anecdotal experience. Further studies are needed to better define the role of chloramphenicol in the modern treatment of infections of critically ill patients. ?

75. Kloramfenikol Primer olarak karacigerden metabolize olur, inaktif formu b?breklerden atilir Karaciger yetmezliginde doz ayarlamasi gerekir. Renal yetmezlikte gerekmez Diren? Kloramfenikol asetiltransferaz Bakteri membran ge?irgenliginde azalma Yan etki Kemik iligi s?presyonu Fatal idiyosenkratik aplastik anemi Chloramphenicol ? Chloramphenicol inhibits protein synthesis by binding reversibly to the 50 S subunit of the bacterial ribosome. Chloramphenicol is generally bacteriostatic, but may be bactericidal in high concentrations or when used against highly susceptible bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Hemophilus influenzae. Its spectrum of activity is broad, including Gram-positive and Gram-negative bacteria, anaerobes, spirochetes, rickettsiae, chlamydiae, and mycoplasma. It is effective parenterally as well as orally (bioavailability 80%) and has excellent tissue penetration. Chloramphenicol is metabolized primarily in the liver, where it is conjugated and excreted in an inactive form by the kidneys. Dose adjustment is required in hepatic, but not renal, insufficiency. Bacteria may develop resistance to chloramphenicol by decreasing their membrane permeability to the drug or by producing an inactivating enzyme, chloramphenicol acetyltransferase. Bone marrow suppression is the most significant adverse effect and may even take the form of a fatal idiosyncratic aplastic anemia. ? Chloramphenicol is still used extensively in Africa and Southeast Asia in the treatment of critically ill patients with bacterial meningitis, brain abscess, melioidosis, rickettsial infections and typhoid fever. In the developed world it is still used occasionally for the treatment of severe infections (e.g. in a case of Stenotrophomonas maltophilia endocarditis of a prosthetic aortic valve in combination with ciprofloxacin [30]) and it may become a useful agent in the treatment of MDR organisms such as VRE or MRSA. In a study of 78 episodes of VRE bacteremia in an academic medical center (including 46 patients located in the ICU) chloramphenicol treatment led to a favorable clinical and microbiological response of approximately 60% and 80%, respectively. Even though hematological abnormalities were noted in one-third of the patients, none could be directly linked to chloramphenicol use [31]. Chloramphenicol has also been administered to treat nosocomial VRE infections in liver transplant recipients [32]. Recently, the successful combined intravenous and intraventricular chloramphenicol treatment of a critically ill patient with subarachnoid hemorrhage and meningitis due to VRE was reported [33]. Of interest, chloramphenicol has also been used successfully for the treatment of VRE infections in a thermal injury patient that developed resistance to quinupristin?dalfopristin [34]. ? Finally, it should be noted that due to its wide antimicrobial spectrum and excellent tissue penetration, chloramphenicol is used sometimes empirically in the hospital setting for the treatment of patients with unknown source of fever. This treatment, however, cannot be widely recommended as it is based on anecdotal experience. Further studies are needed to better define the role of chloramphenicol in the modern treatment of infections of critically ill patients. ?Chloramphenicol ? Chloramphenicol inhibits protein synthesis by binding reversibly to the 50 S subunit of the bacterial ribosome. Chloramphenicol is generally bacteriostatic, but may be bactericidal in high concentrations or when used against highly susceptible bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Hemophilus influenzae. Its spectrum of activity is broad, including Gram-positive and Gram-negative bacteria, anaerobes, spirochetes, rickettsiae, chlamydiae, and mycoplasma. It is effective parenterally as well as orally (bioavailability 80%) and has excellent tissue penetration. Chloramphenicol is metabolized primarily in the liver, where it is conjugated and excreted in an inactive form by the kidneys. Dose adjustment is required in hepatic, but not renal, insufficiency. Bacteria may develop resistance to chloramphenicol by decreasing their membrane permeability to the drug or by producing an inactivating enzyme, chloramphenicol acetyltransferase. Bone marrow suppression is the most significant adverse effect and may even take the form of a fatal idiosyncratic aplastic anemia. ? Chloramphenicol is still used extensively in Africa and Southeast Asia in the treatment of critically ill patients with bacterial meningitis, brain abscess, melioidosis, rickettsial infections and typhoid fever. In the developed world it is still used occasionally for the treatment of severe infections (e.g. in a case of Stenotrophomonas maltophilia endocarditis of a prosthetic aortic valve in combination with ciprofloxacin [30]) and it may become a useful agent in the treatment of MDR organisms such as VRE or MRSA. In a study of 78 episodes of VRE bacteremia in an academic medical center (including 46 patients located in the ICU) chloramphenicol treatment led to a favorable clinical and microbiological response of approximately 60% and 80%, respectively. Even though hematological abnormalities were noted in one-third of the patients, none could be directly linked to chloramphenicol use [31]. Chloramphenicol has also been administered to treat nosocomial VRE infections in liver transplant recipients [32]. Recently, the successful combined intravenous and intraventricular chloramphenicol treatment of a critically ill patient with subarachnoid hemorrhage and meningitis due to VRE was reported [33]. Of interest, chloramphenicol has also been used successfully for the treatment of VRE infections in a thermal injury patient that developed resistance to quinupristin?dalfopristin [34]. ? Finally, it should be noted that due to its wide antimicrobial spectrum and excellent tissue penetration, chloramphenicol is used sometimes empirically in the hospital setting for the treatment of patients with unknown source of fever. This treatment, however, cannot be widely recommended as it is based on anecdotal experience. Further studies are needed to better define the role of chloramphenicol in the modern treatment of infections of critically ill patients. ?

76. Kloramfenikol Afrika ve G?neydogu Asya?da hala kullaniliyor Bakteriyel menenjit, beyin apsesi Melidiosis Riketsiyal hastaliklar Tifo Diger ?lkelerde Diren?li ciddi infeksiyonlarin tedavisi Stenotrophomonas maltophilia endokarditi (Siprofloksasin ile kombine) VRE, MRSA bakteremileri, menenjitleri Chloramphenicol is still used extensively in Africa and Southeast Asia in the treatment of critically ill patients with bacterial meningitis, brain abscess, melioidosis, rickettsial infections and typhoid fever. In the developed world it is still used occasionally for the treatment of severe infections (e.g. in a case of Stenotrophomonas maltophilia endocarditis of a prosthetic aortic valve in combination with ciprofloxacin [30]) and it may become a useful agent in the treatment of MDR organisms such as VRE or MRSA. In a study of 78 episodes of VRE bacteremia in an academic medical center (including 46 patients located in the ICU) chloramphenicol treatment led to a favorable clinical and microbiological response of approximately 60% and 80%, respectively. Even though hematological abnormalities were noted in one-third of the patients, none could be directly linked to chloramphenicol use [31]. Chloramphenicol has also been administered to treat nosocomial VRE infections in liver transplant recipients [32]. Recently, the successful combined intravenous and intraventricular chloramphenicol treatment of a critically ill patient with subarachnoid hemorrhage and meningitis due to VRE was reported [33]. Of interest, chloramphenicol has also been used successfully for the treatment of VRE infections in a thermal injury patient that developed resistance to quinupristin?dalfopristin [34]. ? Finally, it should be noted that due to its wide antimicrobial spectrum and excellent tissue penetration, chloramphenicol is used sometimes empirically in the hospital setting for the treatment of patients with unknown source of fever. This treatment, however, cannot be widely recommended as it is based on anecdotal experience. Further studies are needed to better define the role of chloramphenicol in the modern treatment of infections of critically ill patients.? Chloramphenicol is still used extensively in Africa and Southeast Asia in the treatment of critically ill patients with bacterial meningitis, brain abscess, melioidosis, rickettsial infections and typhoid fever. In the developed world it is still used occasionally for the treatment of severe infections (e.g. in a case of Stenotrophomonas maltophilia endocarditis of a prosthetic aortic valve in combination with ciprofloxacin [30]) and it may become a useful agent in the treatment of MDR organisms such as VRE or MRSA. In a study of 78 episodes of VRE bacteremia in an academic medical center (including 46 patients located in the ICU) chloramphenicol treatment led to a favorable clinical and microbiological response of approximately 60% and 80%, respectively. Even though hematological abnormalities were noted in one-third of the patients, none could be directly linked to chloramphenicol use [31]. Chloramphenicol has also been administered to treat nosocomial VRE infections in liver transplant recipients [32]. Recently, the successful combined intravenous and intraventricular chloramphenicol treatment of a critically ill patient with subarachnoid hemorrhage and meningitis due to VRE was reported [33]. Of interest, chloramphenicol has also been used successfully for the treatment of VRE infections in a thermal injury patient that developed resistance to quinupristin?dalfopristin [34]. ? Finally, it should be noted that due to its wide antimicrobial spectrum and excellent tissue penetration, chloramphenicol is used sometimes empirically in the hospital setting for the treatment of patients with unknown source of fever. This treatment, however, cannot be widely recommended as it is based on anecdotal experience. Further studies are needed to better define the role of chloramphenicol in the modern treatment of infections of critically ill patients.?

77. Diger antibiyotikler Trimethoprim/sulfamethoxazole S. maltophilia?ya m?kemmel etkinlik Pneumocystis jiroveci Toplum k?kenli MRSA Minosiklin Ikinci kusak tetrasiklin Rifampisin ve diger bazi antibiyotiklerle kombinasyonu MDR A. baumannii tedavisinde Basitrasin Polipeptid antibiyotik Kritik hastalarin gastrointestinal sisteminden VRE eradikasyonu i?in kullanilir Other antibiotics ? Even though a detailed description is beyond the scope and the space limitations of this review, it should be emphasized that a number of other old antibiotics are also useful in the critical care setting. For example, trimethoprim/sulfamethoxazole remains an important antibiotic in the critical care setting, as it has excellent activity against S. maltophilia [35], is the agent of choice against Pneumocystis jiroveci, an important cause of respiratory failure and subsequent ICU admission of immunocompromised patients [36], and is currently used increasingly for the management of infections caused by community-acquired MRSA [37?]. Since its use may be associated with disorders that appear often in critically ill patients, such as hematological toxicity (i.e. thrombocytopenia), hepatic dysfunction and hyperkalemia, close monitoring for these adverse events is warranted. Minocycline, a second-generation tetracycline used mainly for the treatment of acne, and rifampin (in combination with other antibiotics) have shown activity against some MDR strains of A. baumannii [38,39?]. Finally, bacitracin, a polypeptide antibiotic, is occasionally used for VRE eradication from the gastrointestinal tract of severely ill patients [40,41], novobiocin, a DNA gyrase inhibitor, has been shown (in combination with rifampin) to decrease the infectious complications associated with vascular catheters (namely, insertion-site infections and catheter-associated bacteremias) in a high-risk population of melanoma patients treated with interleukin-2, interferon-[alpha] and chemotherapy [42], and nitrofurantoin, a urinary antiseptic, was recently shown to be effective in vitro against 99.4% of 697 VRE urinary isolates isolated in 38 medical centers in the United States and Canada and, therefore, it may have a role in the treatment of VRE-associated urinary tract infections [43]. Other antibiotics ? Even though a detailed description is beyond the scope and the space limitations of this review, it should be emphasized that a number of other old antibiotics are also useful in the critical care setting. For example, trimethoprim/sulfamethoxazole remains an important antibiotic in the critical care setting, as it has excellent activity against S. maltophilia [35], is the agent of choice against Pneumocystis jiroveci, an important cause of respiratory failure and subsequent ICU admission of immunocompromised patients [36], and is currently used increasingly for the management of infections caused by community-acquired MRSA [37?]. Since its use may be associated with disorders that appear often in critically ill patients, such as hematological toxicity (i.e. thrombocytopenia), hepatic dysfunction and hyperkalemia, close monitoring for these adverse events is warranted. Minocycline, a second-generation tetracycline used mainly for the treatment of acne, and rifampin (in combination with other antibiotics) have shown activity against some MDR strains of A. baumannii [38,39?]. Finally, bacitracin, a polypeptide antibiotic, is occasionally used for VRE eradication from the gastrointestinal tract of severely ill patients [40,41], novobiocin, a DNA gyrase inhibitor, has been shown (in combination with rifampin) to decrease the infectious complications associated with vascular catheters (namely, insertion-site infections and catheter-associated bacteremias) in a high-risk population of melanoma patients treated with interleukin-2, interferon-[alpha] and chemotherapy [42], and nitrofurantoin, a urinary antiseptic, was recently shown to be effective in vitro against 99.4% of 697 VRE urinary isolates isolated in 38 medical centers in the United States and Canada and, therefore, it may have a role in the treatment of VRE-associated urinary tract infections [43].

78. Diger antibiyotikler Novobiosin DNA giraz inhibit?r? Rifampisin ile kombinasyonu kateter iliskili bakteremi ve kateter iliskili diger infeksiy?z komplikasyonlari azaltir Nitrofurantoin ?riner antiseptik VRE ?riner izolatlara %99.4 etkili VRE iliskili ?SI tedavisinde Other antibiotics ? Even though a detailed description is beyond the scope and the space limitations of this review, it should be emphasized that a number of other old antibiotics are also useful in the critical care setting. For example, trimethoprim/sulfamethoxazole remains an important antibiotic in the critical care setting, as it has excellent activity against S. maltophilia [35], is the agent of choice against Pneumocystis jiroveci, an important cause of respiratory failure and subsequent ICU admission of immunocompromised patients [36], and is currently used increasingly for the management of infections caused by community-acquired MRSA [37?]. Since its use may be associated with disorders that appear often in critically ill patients, such as hematological toxicity (i.e. thrombocytopenia), hepatic dysfunction and hyperkalemia, close monitoring for these adverse events is warranted. Minocycline, a second-generation tetracycline used mainly for the treatment of acne, and rifampin (in combination with other antibiotics) have shown activity against some MDR strains of A. baumannii [38,39?]. Finally, bacitracin, a polypeptide antibiotic, is occasionally used for VRE eradication from the gastrointestinal tract of severely ill patients [40,41], novobiocin, a DNA gyrase inhibitor, has been shown (in combination with rifampin) to decrease the infectious complications associated with vascular catheters (namely, insertion-site infections and catheter-associated bacteremias) in a high-risk population of melanoma patients treated with interleukin-2, interferon-[alpha] and chemotherapy [42], and nitrofurantoin, a urinary antiseptic, was recently shown to be effective in vitro against 99.4% of 697 VRE urinary isolates isolated in 38 medical centers in the United States and Canada and, therefore, it may have a role in the treatment of VRE-associated urinary tract infections [43]. Other antibiotics ? Even though a detailed description is beyond the scope and the space limitations of this review, it should be emphasized that a number of other old antibiotics are also useful in the critical care setting. For example, trimethoprim/sulfamethoxazole remains an important antibiotic in the critical care setting, as it has excellent activity against S. maltophilia [35], is the agent of choice against Pneumocystis jiroveci, an important cause of respiratory failure and subsequent ICU admission of immunocompromised patients [36], and is currently used increasingly for the management of infections caused by community-acquired MRSA [37?]. Since its use may be associated with disorders that appear often in critically ill patients, such as hematological toxicity (i.e. thrombocytopenia), hepatic dysfunction and hyperkalemia, close monitoring for these adverse events is warranted. Minocycline, a second-generation tetracycline used mainly for the treatment of acne, and rifampin (in combination with other antibiotics) have shown activity against some MDR strains of A. baumannii [38,39?]. Finally, bacitracin, a polypeptide antibiotic, is occasionally used for VRE eradication from the gastrointestinal tract of severely ill patients [40,41], novobiocin, a DNA gyrase inhibitor, has been shown (in combination with rifampin) to decrease the infectious complications associated with vascular catheters (namely, insertion-site infections and catheter-associated bacteremias) in a high-risk population of melanoma patients treated with interleukin-2, interferon-[alpha] and chemotherapy [42], and nitrofurantoin, a urinary antiseptic, was recently shown to be effective in vitro against 99.4% of 697 VRE urinary isolates isolated in 38 medical centers in the United States and Canada and, therefore, it may have a role in the treatment of VRE-associated urinary tract infections [43].

79. Sonu? ? ?Eskiye ragbet olsa bit pazarina nur yagardi?


Other Related Presentations

Copyright © 2014 SlideServe. All rights reserved | Powered By DigitalOfficePro