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Betalactam Antibiotics and LRTI

Betalactam Antibiotics and LRTI. Oğuz Kılınç Dokuz Eylul University School of Medicine Chest Dept. oguz.kilinc@deu.edu.tr. Conflict of Interest (Last 3 years). Congress sponsorship Abdi İbrahim Actavis Boehringer İngelheim Chiesi GSK Novartis Pfizer Advisory Board Bayer

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Betalactam Antibiotics and LRTI

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  1. Betalactam Antibiotics and LRTI Oğuz Kılınç Dokuz Eylul University School of Medicine Chest Dept. oguz.kilinc@deu.edu.tr

  2. Conflict of Interest(Last 3 years) • Congress sponsorship • Abdi İbrahim • Actavis • Boehringer İngelheim • Chiesi • GSK • Novartis • Pfizer • Advisory Board • Bayer • Boehringer İngelheim • Chiesi • GSK • Novartis • Pfizer • Lecturer Fee • Astra • Bayer • Boehringer İngelheim • GSK • Novartis • Pfizer • Clnical Research Support • Astra • Bayer • GSK • Novartis • Pfizer • Tütün endüstrisiyle hiçbir ilişkim yoktur.

  3. Lecture Plan • What is LRTI? • Caracteristics of betalactam antibiotics • Betalactam antibiotics and LRTI?

  4. What is LRTI? • CAP • AECOPD • AE of bronchiectasis • Acute bronchitis • M Woodhead. Clin Microbiol Infect 2011; 17(Suppl. 6): E1–E59

  5. Betalactam antibiotics • Penicillin • Cephalosporins • Carbapenems • Monobactams • Betalactamase inhibitors http://yunus.hacettepe.edu.tr/~pkelicen erişim tarihi 18.03.2012

  6. Betalactams * Negligible antimicrobial activity when given alone http://yunus.hacettepe.edu.tr/~pkelicen downloded 18.03.2012

  7. Betalactams http://yunus.hacettepe.edu.tr/~pkelicen erişim tarihi 18.03.2012

  8. Betalactams http://yunus.hacettepe.edu.tr/~pkelicen erişim tarihi 18.03.2012

  9. Resistans mechanism to penicillins • Inactivation of betalactam body because of betalactamase • Betalactamase secretion to periplasmic space (S. aureus ve Gram (-) ) • Out of membrane (Gram (+)) • Decrase of PBP affinity • Decrase of cell wall permiability • Kayaalp O. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji, 10. Baskı, Hacettepe Taş, 2002.

  10. Clinical caracteristics of cephalosporins • A part of patients who have penicilline allergy, • Betalactamase (+) S. aureus infections • PBP • Kayaalp O. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji, 10. Baskı, Hacettepe Taş, 2002.

  11. Carbapenems • High affinty to PBP 1 and 2 • Resistant to betalaktamase • Bacterisid for betalactam resistans bacteria • Kayaalp O. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji, 10. Baskı, Hacettepe Taş, 2002.

  12. Aetiology of LRTI in the community

  13. Aetiology of CAP(Outpatient)

  14. Betalactamase resistans in Turkey?S. pneumoniae • EARSS (2008) • 32 European country (Turkey data) invasiv S. pneumonia • PNSP %34

  15. S. pneumoniae Penicilline resistans- effect of therapy? • PO treatment • MIC • Sensitive (≤ 0.06 mg/L), intermediate (0.12- 1 mg/L), resistans ( ≥2 mg/L) • Parenteral treatment • Sensitive (≤ 2 mg/L), intermediate (4 mg/L), resistans ( ≥8 mg/L) • Good news for clinicans

  16. Pneumococci resistans in Turkey Gülmez D ve ark. ECCMID Congress 2010

  17. H. influenzae betalactam resistans • EARSS study • Main resistans mechanism beta-laktamase production (mean %7.6) • Cephalosporin and betalactamase inhibitor + betalactam • PBP 3 coding gen (BLNAR) • Resistans to aminopenicilline and cephalosporine

  18. M. catarrhalis –betalactam resistans • No change since 1999 . • All species resistans to ampicillin, amoxacilline, piperacilline and penicilline • BRO-1, BRO- 2 type betalaktamase resistans • betalactam betalactamase inhibitor.

  19. M. pneumoniae- betalactam resistans • Resistans to all betalactams

  20. CA- MRSA • Resistans to all betalactams

  21. Treatment • Penicilline G 3.2 M U x 6 IV • Ceftriaxone 1g x 2 IV/IM • Cefotaxime 2g x 4 IV • Amoxacilline+clavulanic acid 2g/125mg x 2 PO

  22. Double blind, randomized controlled, monoterapy study meta-analysis • 18 study, 6749 patients • Mild and moderate CAP Mills GD ve ark. BMJ 2005

  23. Mills GD ve ark. BMJ 2005

  24. TTS CAP guideline • Grup 1 • 1A • Amoksisilin veya Makrolid • 1B • 2.3. kuşak oral sefalosporin veya KAM +/- Makrolid/Doksisiklin • Grup 2 • 3. kuşak antipseudomonas olmayan sefalosporin veya betalaktam+ betalaktamaz inhibitörlü aminopenisilin + Makrolid /quinolon • Grup 3 • 3A • 3 generation non- pseudomonas cephalosporin or betalactam+ betalactamase inhibitor + Macrolid or quinolon • 3B • Antipseudomonas betalactam+ciprofloksasin or aminoglikozid + Macrolid

  25. Wrap up • We have to know what we treat • Surveillance of resistans rate • Appropiate treatment

  26. Teşekkürler

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